cssi/SciSciGPT-SciSciNet huggingface dataset:
Structure of the Escherichia coli Fis-DNA complex probed by protein conjugated with 1,10-phenanthroline copper(I) complex

Abstract The Escherichia coli Fis (factor for inversion stimulation) protein functions in many diverse biological systems including recombination, transcription, and DNA replication. Although Fis is a site-specific DNA-binding protein, it lacks a well-defined consensus recognition sequence. The electrophoretic mobility of Fis-DNA complexes, along with considerations of the Fis crystal structure, indicates that significant deformation of DNA occurs upon Fis binding. To investigate the structure of Fis-DNA complexes, the chemical nuclease 1,10-phenanthroline-copper complex (OP-Cu) has been linked to four specific sites within the Fis DNA-binding domain. Two of these Fis-OP derivatives were active in cleaving DNA. The scission patterns obtained on four different Fis binding sites indicate that Fis positions itself on these highly divergent DNA sequences in a very similar fashion. The patterns of cleavage of a derivative at Asn-98 generally support a model of a Fis-DNA complex that contains specific bends within the core-recognition sequence. Data from a second Fis-OP derivative at Asn-73 provides evidence for greater wrapping of flanking DNA around the sides of the Fis protein than was previously postulated. The cleavage efficiency of flanking segments varies, suggesting that the extent of DNA wrapping is sequence dependent. Specific amino acids on Fis are implicated in promoting this DNA wrapping.
Anisotropies in peripheral vernier acuity

Vernier acuity for short horizontal, vertical and oblique target lines was measured in many locations in the periphery of the visual field in normal human observers. In the 10 deg periphery, the average alignment threshold with oblique vernier lines in eight locations for three observers was 2.29 times higher than that with vertical and horizontal target lines. This oblique effect was found everywhere in the visual field. Similar conclusions are drawn for configurations in which the lines were replaced by just their distal endpoints, but here, additionally, performance was distinctly better when the dot pair was collinear with the fixation point, i.e. oriented radially, than when it was oriented tangentially. Both for vernier lines and for dot pairs, in all observers, horizontal configurations showed somewhat better thresholds than vertical ones. These results suggest an inherent pattern of connectivity throughout the visual field favoring processing in the cardinal orientations over the obliques, the radial over the tangential and, to a limited extent, the horizontal over the vertical.
Inferring migration of CO2 plume using injection data and a probabilistic history matching approach

Abstract Large-scale implementation of geologic carbon storage (GCS) will require reliable techniques for monitoring the movement of the CO2 plume in the subsurface. The movement of CO2 plumes beyond the region permitted for storage will be of particular interest both to regulators and to operators. However, the cost of many monitoring technologies, such as time-lapse seismic, limits their application. Given that injection data (pressures, rates) from wells are readily available and inexpensive, we examine whether they can be used as a viable alternative for monitoring and predicting plume migration. In this paper, we have implemented a probabilistic history matching approach to creating models of the aquifer for predicting the movement of the CO2 plume. The geologic property of interest for example hydraulic conductivity is updated conditioned to geological information and injection pressures. The resultant aquifer model which is geologically consistent can be used to reliably predict the movement of the CO2 plume in the subsurface. We tailor the method to CO2 sequestration by considering only injection data in the matching process. We also introduce a two-step approach to stochastically simulate high-permeability features such as oriented sets of natural fractures that occupy only a small fraction of the storage formation. We illustrate the approach by applying it to data from the In Salah Gas project. The final history-matched models contain high permeability features consistent with the field observation of rapid arrival of injected CO2 at a suspended well and with surface deformation data obtained by remote sensing. We conclude that the approach can provide a probabilistic assessment of plume migration at the field scale.
Evaluation of the Esophageal-Fistula Cannula and Hand-Clip Methods for Sampling Coastal Bermudagrass Pastures

Abstract Two management treatments of Coastal Bermudagrass were used to compare esophageal-fistula cannula and hand-clip (5 cm height) methods of sampling pasture forage and to determine relationships between chemical components and animal responses. Forage samples were collected on the first, fourth, and seventh days of each week for ten consecutive weeks and crude protein, acid-detergent-fiber (ADF), lignin, and ash contents determined. Milk production, milk composition, forage digestibility, forage dry matter intakes, and weight changes were determined for six cows per treatment. Forage from Treatment 1 (mowed at 10.2 cm) was higher (P 0.05) in acid-detergent-fiber values between days or in the milk production, digestibility of dry matter, or intake of Coastal forage by cows grazing the two management treatments.
Dynamics and symmetries for pure phase mass matrices

We explore Higgs field interactions that can produce fermion mass matrices in the highly textured symmetric pure phase form, a form consistent with phenomenology. The potentials that can be made consistent with the symmetric pure phase form imply a simple set of discrete symmetries in the structure of the Lagrangian, symmetries closely connected to the hierarchical structure of fermion masses and the Cabibbo-Kobayashi-Maskawa matrix. {copyright} {ital 1998} {ital The American Physical Society}
Urogynecology: comments and caveats.

Historically, the routine workup of the incontinent woman has focused on clinical parameters including , history, pelvic examination, cotton swab test, and radiographic imaging of the bladder and urethra. Data are presented to support the concept that urinary symptoms and pelvic findings do not accurately define the causes of incontinence. Because urinary incontinence is both a dysfunctional and a structural problem, evaluation of the urodynamic response of the lower urinary tract should be part of the workup of the incontinent woman.
Upper limits on neutron and γ-ray emission from cold fusion

Neutron and γ-ray emission from a variety of electrochemical cells (running continuously for up to two weeks) have been measured using a sensitive detection system with a very low background. Titanium alloy powder deuterided at room temperature and high pressure was also used for comparison. No statistically significant deviation from the background was observed in either γ-ray or neutron detectors. The estimated neutron flux in this experiment is at least a factor of 50 times smaller than that reported by Jones et al. and about one million times smaller than that reported by Fleischmann et al. The results suggest that a significant fraction of the observed neutron events are associated with cosmic rays.
Evaluation of porfimer sodium fluorescence for measuring tissue transformation

Background. Neoplastic tissue can be detected by its increased fluorescence compared with surrounding normal tissue after the injection of the tumor-localizing compound porfimer sodium (Photofrin; Quadra Logic Technologies, Vancouver, BC, Canada). In vivo fluorescence photometry is a nonimaging photodetector technique that detects specific 690 nm fluorescence of the porphyrin by subtracting nonspecific 612 nm excitation from 630 nm excitation. The technique was applied in the developmental stages of the 9,10 dimethyl-l,2-benzanthracene (DMBA)-induced hamster buccal cheek pouch carcinoma model to (1) quantitate and characterize porfimer sodium fluorescence and uptake as it relates to lesion progression and biochemical changes and (2) determine whether porfimer sodium-induced fluorescence will vary with promotional and inhibitory stimuli. Methods. Groups of Syrian Golden hamsters had their cheek pouch buccal mucosa exposed to a 0.5% DMBA in acetone three times per week for 6 weeks (premalignant lesions), 12 weeks (squamous cell carcinomas), or other specified durations. The rate of malignant transformation was either promoted (by either carbon dioxide laser incision or continued DMBA application) or inhibited (by the administration of either somatostatin analogue RC-160 [D-Phe-Cys-Tyr-D-TrpLys-Val-Cys-Trp-NH,] or bombesin antagonist RC-3095 [ D - Tpi - Gln - Trp - Ala - Val - Gly -His - Leu$ (CH,NH) LeuNH,]). Groups of DMBA-exposed hamsters were subsequently injected with 1.0 mg/kg of porfimer sodium during the various stages of tumor development. Twentyfour hours after injection, fluorescence levels were measured by in vivo fluorescence photometry. Samples of tumors, dysplastic mucosal tissue, and normal-appearing oral mucosa were biopsied and used for either tissue extraction assays, histopathologic examination, or tyrosine kinase activity assay as an index of rate of transformation. Results. Results demonstrated that porfimer sodium is retained in DMBA-treated tissue. Fluorescence is completely accounted for by porfimer sodium uptake. The duration of exposure to carcinogen is proportional to porfimer sodium fluorescence. This relationship establishes that premalignant lesions can be distinguished from normal tissue by porfimer sodium uptake and fluorescence. The changes in increased tyrosine kinase activity paralleled the increase in porfimer sodium fluorescence. Alterations in the rate of tissue transformation produced equivalent alterations in porfimer sodium-induced fluorescence. Conclusions. These results suggest that porfimer sodium uptake and fluorescence can be used in a prognostic manner to diagnose and determine the course of transformation of individual lesions. Cancer 1993; 723068-77.
Do clinical variables predict pathologic radiographs in the first episode of wheezing

Objective: To determine if clinical variables assessed in relation to Albuterol aerosol treatments accurately identify children with pathologic radiographs during their initial episode of bronchospasm. Methods: A prospective convenience sample of children with a first episode of wheezing. Data collected included demographics, baseline and post-treatment clinical score and physical examination, number of aerosols, requirement for supplemental oxygen, and disposition. Chest radiographs were obtained and interpreted, and patients were divided into 2 groups based on a pathologic versus nonpathologic radiograph interpretation. X 2 testing was performed for categoric variables, and the student t test was performed for continuous variables. A discriminant analysis was used to develop a model. Results: Pathologic radiographs were identified in 61 patients (9%). Between groups, a significant difference was noted for pretreatment oxygen saturation only. Clinical score, respiratory rate, and presence of rales both pretreatment and post-treatment were not significantly different between groups. The discriminant analysis correctly predicted 90% of nonpathologic radiographs but only 15% of pathologic radiographs. Conclusions: Clinical variables, either isolated or as components of a model, could not identify all children with pathologic radiographs.
Surgical excision of eroded mesh after prior abdominal sacrocolpopexy

Objective We previously described an endoscopic-assisted transvaginal mesh excision technique. This study compares surgical outcomes after transvaginal mesh excision vs endoscopic-assisted transvaginal mesh excision. In addition, we reviewed our postoperative outcomes with excision via laparotomy. Study Design This was an inclusive retrospective analysis of patients presenting to our institution from 1997 to 2006 for surgical management of vaginal erosion of permanent mesh after sacrocolpopexy. Three techniques were utilized: transvaginal, endoscopic-assisted transvaginal, and laparotomy. For the patients undergoing transvaginal excision, data recorded included number and type of excisions performed, number of prior excisions performed at outside facilities, intraoperative and postoperative complications (including blood transfusions, pelvic abscess, or bowel complications), use of postoperative antibiotics, persistent symptoms of vaginal bleeding and discharge at follow-up, and demographic characteristics. The intraoperative and postoperative complications and the postoperative symptoms were recorded for the laparotomy cases. Results Thirty-one patients underwent transvaginal mesh excision during this time period: 17 endoscopic-assisted transvaginal and 14 transvaginal without endoscope assistance. In addition, a total of 7 patients underwent abdominal excision via laparotomy. Comparison of the 2 vaginal methods revealed no difference in the demographics or success rate, with success defined as no symptoms at follow-up. Endoscopic-assisted transvaginal excision was successful in 7 of 17 patients and transvaginal without endoscopic assistance in 9 of 13 patients (1 patient excluded for lack of follow-up data) for a total vaginal success rate of 53.3%. No intraoperative and only minor postoperative complications occurred with either vaginal method. Three patients underwent 3 vaginal attempts to achieve complete symptom resolution. The average follow-up time for the entire vaginal group was 14 months. Seven patients ultimately required abdominal excision and all had symptom resolution, however, not without complications. Two patients had bowel injury during lysis of adhesions requiring bowel resection in 1 case and repair in another, 1 had a postoperative wound infection with breakdown, 1 was readmitted for postoperative fever requiring antibiotics, and 1 had an acute coronary syndrome requiring transfer to the cardiology service. Conclusion Transvaginal excision of mesh with or without endoscopy appears to be a safe and less invasive method for excision of eroded vaginal mesh after prior abdominal sacrocolpopexy. Up to 3 vaginal excision attempts may be necessary to achieve symptom resolution, and complete removal of mesh will likely improve outcomes with the transvaginal technique. Although abdominal excision can be considered the gold standard for excision of eroded mesh, it is not without potentially increased morbidity.
Finite-size effects on plasmonlike excitations in relativistic heavy-ion collisions.

The modifications of plasmonlike excitations in hot hadronic or quark-gluon matter due to the finite size of the systems that will be produced in relativistic heavy-ion collisions are investigated. It is shown that the relevant parameter is {ital RM}{sup 2}/{vert bar}{bold q}{vert bar} where {ital R} is the size of the system, {ital M} is the mass of the plasmon in an infinite system, and {bold q} is its three-momentum in the plasmon. If {ital RM}{sup 2}/{vert bar}{bold q}{vert bar}{much lt}1, the plasmon excitations will not be produced. This has important implications for plasmons generated in heavy-ion collisions by electromagnetic interactions which have been suggested by some authors.
Prolactin and Male Reproduction

Elevated levels of prolactin(PRL) are associated with gonadal dysfunction in men and women, but the relationship between PRL levels and gonadal activity is best defined in women. The purpose of this review is to summarize and discuss the influence of PRL on the male reproductive function in normaprolactinemia and to describe the clinical, diagnostic, and therapeutic aspects of the male hyperprolactinemia syndrome as related to sexual dysfunction and infertility.
Intracranial Imaging of Uncommon Diseases Is More Frequently Reported in Clinical Publications Than in Radiology Publications

BACKGROUND AND PURPOSE: Descriptions of uncommon diseases with intracranial imaging abnormalities are often difficult to find in the radiology literature. We hypothesized that reported imaging findings of such conditions in the recent literature were more frequent in clinical compared with radiology journals. MATERIALS AND METHODS: PubMed searches from December 1, 2007 to December 1, 2012 were performed for 5 uncommon CNS diseases with intracranial imaging manifestations: 1) Susac syndrome; 2) amyloid β–related angiitis; 3) Parry-Romberg syndrome/en coup de sabre; 4) transient lesion of the splenium of the corpus callosum; and 5) reversible cerebral vasoconstriction syndrome. Articles were classified as a case report, case series, or original research. Journals were categorized as radiology or clinical. The 1- and 5-year Impact Factors of the journals were recorded. RESULTS: Two hundred two articles were identified for the 5 diseases, including 151 (74%) case reports, 26 case series (13%), and 25 original research articles (13%); 179 (89%) were published in nonradiology journals, compared with 23 (11%) in radiology journals. There was no significant difference between the mean 1- and 5-year Impact Factors of the radiology and clinical journals. CONCLUSIONS: Recent reports of the selected uncommon diseases with intracranial manifestations are more frequent in clinical journals when compared with dedicated radiology publications. Most publications are case reports. Radiologists should review both radiology and clinical journals when reviewing imaging features of uncommon diseases affecting the brain. Lack of reporting on such disease in the radiology literature may have significant practice, educational, and research implications for the radiology community.
Imaging the pathophysiology of major depressive disorder - from localist models to circuit-based analysis

The neuroimaging literature of Major Depressive Disorder (MDD) has grown substantially over the last several decades, facilitating great advances in the identification of specific brain regions, neurotransmitter systems and networks associated with depressive illness. Despite this progress, fundamental questions remain about the pathophysiology and etiology of MDD. More importantly, this body of work has yet to directly influence clinical practice. It has long been a goal for the fields of clinical psychology and psychiatry to have a means of making objective diagnoses of mental disorders. Frustratingly little movement has been achieved on this front, however, and the 'gold-standard’ of diagnostic validity and reliability remains expert consensus. In light of this challenge, the focus of the current review is to provide a critical summary of key findings from different neuroimaging approaches in MDD research, including structural, functional and neurochemical imaging studies. Following this summary, we discuss some of the current conceptual obstacles to better understanding the pathophysiology of depression, and conclude with recommendations for future neuroimaging research.
Enhanced Coercivity in Melt-Spun Sm(Co, Fe, Cu)5 Ribbons by Low Temperature Aging

The authors studied the influence of microstructure and grain size, as well as Curie temperature, on the low-temperature aged Sm(Co0.45Cu0.4Fe0.15)5 alloy in relation to enhanced coercivity. Melt-spinning has been employed in order to achieved a wide range of grain sizes from micro- to nanometer level. XRD and TEM analysis were used to study the structure of as-spun ribbons and SQUID magnetometer was used to determine the magnetic hysteresis parameters. Results showed that the enhanced coercivity of aged ribbons is higher than that one obtained in 1:5 microstructure aged magnets prior to the changes in Curie temperature.
3D cardiac motion tracking using Robust Point Matching and meshless deformable models

We propose a novel 3D motion estimation approach integrating the robust point matching (RPM) and meshless deformable models. In our study, we first use the Gabor filters to generate phase maps of short axis (SA) and long axis (LA) tagged MRI sequences. Then we use the RPM to track the heart motion sparsely at intersections of tag grids in these image sequences, using both intensity gradient and phase information. Next, the new meshless deformable model is used to recover the dense 3D motion of the myocardium temporally during the cardiac cycle. The deformable model is driven by external forces computed at tag intersections based on the RPM motion tracking and keeps a consistent but flexible topology during the deformation using internal constraint forces calculated by the moving least squares (MLS) method. The deformable model recovers the global deformation of the LV such as rotation, contraction and twisting by integrating global deformation parameters over the volume. The new model avoids the singularity problem of mesh-based deformable models and is capable of tracking deformation efficiently with the sparse external forces derived from tagging line intersections. We test the performance of the new approach on in vivo heart data of healthy subjects and patients. The experimental results show that our new method can fully recover the myocardium motion and strain in 3D.
Test challenges for deep sub-micron technologies

The use of deep submicron process technologies presents several new challenges in the area of manufacturing test. While a significant body of work has been devoted to identifying and investigating design challenges in nanometer technologies, the impact on test strategies and methodologies is still not well understood. This paper highlights the challenges to current test methodologies arising from technology driven trends, and will present an overview of emerging techniques that address deep submicron test challenges.
A rearranged EP300 gene in the human B-cell lymphoma cell line RC-K8 encodes a disabled transcriptional co-activator that contributes to cell growth and oncogenicity.

Human diffuse large B-cell lymphoma cell line RC-K8 has an altered EP300 locus that encodes a C-terminally truncated histone acetyltransferase (HAT) protein (p300ΔC). We now show that p300ΔC contains 1047 N-terminal amino acids of p300 fused to 25 amino acids encoded by sequences from chromosome 6. Over-expressed p300ΔC localized to nuclear subdomains and interacted with transcription factor REL. p300ΔC did not function as a co-activator for REL-directed transactivation, and blocked the ability of wild-type p300 to enhance transcriptional activation by REL. Knock down of p300ΔC in RC-K8 cells reduced their growth in both liquid culture and soft agar. Truncations of p300 were not found in eight other B-lymphoma cell lines. These results suggest that p300ΔC contributes to the oncogenic state of RC-K8 cells by acting as a defective co-activator.
Design and Analysis of Agents for Supply Chain Management: Experiences From the Trading Agent Competition

AbstractRapid globalization in recent decades and the consequent demands make it essential for supply chains (SCs) and their managers to account for real-world dynamics in managing businesses to successfully compete and emerge as market leaders. The vast majority of SC models discussed in the literature are Ȝstaticȝ greatly stylized, generally local and decision specific. While they present a number of important insights into the working of SCs, they are constricted by the model-related assumptions and replication-related problems. The dynamic nature of the business environment is subjecting SC players to a much more volatile market environment than ever before. Agent-based solutions are particularly relevant in this changing market context. Agent-based approach for supply chain management (SCM) was given a boost with the unveiling of the ȜTAC-SCMȝ competition in 2003 by Carnegie Mellon University and the Swedish Institute of Computer Science through the Trading Agent Competition (TAC). Based on our compe...
Characterization of Catalyst Materials for Production of Aerospace Fuels

Due to environmental, economic, and security issues, there is a greater need for cleaner alternative fuels. There will undoubtedly be a shift from crude oil to non-petroleum sources as a feedstock for aviation (and other transportation) fuels. Additionally, efforts are concentrated on reducing costs coupled with fuel production from non-conventional sources. One solution to this issue is Fischer-Tropsch gas-to-liquid technology. Fischer-Tropsch processing of synthesis gas (CO/H2) produces a complex product stream of paraffins, olefins, and oxygenated compounds such as alcohols and aldehydes. The Fisher-Tropsch process can produce a cleaner diesel oil fraction with a high cetane number (typically above 70) without any sulfur or aromatic compounds. This process is most commonly catalyzed by heterogeneous (in this case, silver and platinum) catalysts composed of cobalt supported on alumina or unsupported alloyed iron powders. Physisorption, chemisorptions, scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) are described to better understand the potential performance of Fischer-Tropsch cobalt on alumina catalysts promoted with silver and platinum. The overall goal is to preferentially produce C8 to C18 paraffin compounds for use as aerospace fuels. Progress towards this goal will eventually be updated and achieved by a more thorough understanding of the characterization of catalyst materials. This work was supported by NASA s Subsonic Fixed Wing and In-situ Resource Utilization projects.
ANALYSIS OF DIRECT P(Y)-CODE ACQUISITION

Global Positioning System (GPS) signal acquisition consists of a two-dimensional search in a time/frequency space to synchronize a receiver-generated reference signal with the received GPS signal in code phase and fre- quency. User uncertainties in code phase and frequency offsets determine the size of the region to be searched, and hence, the code acquisition time. Encrypted P(Y) code, transmitted on L 1 and L2 fiequen- ties, provides more precise (16 m - spherical error proba- ble (SEP)) user positioning inherently more jamming immunity than does C/A code. The purpose of this study is to explore and use existing signal detection concepts to quantify the time to achieve direct acquisition of the P(Y) code in a jamming environ- ment. Of particular interest is the mitigating effect paral- lel processing has in shrinking acquisition time in the presence of initial (receiver) position, time, velocity, and frequency errors and/or uncertainties.
A randomized comparison of total or supracervical hysterectomy: surgical complications and clinical outcomes

Abstract Objective To compare surgical complications and clinical outcomes after total versus supracervical abdominal hysterectomy for control of abnormal uterine bleeding, symptomatic uterine leiomyomata, or both. Methods We conducted a randomized intervention trial in four US clinical centers among 135 patients who had abdominal hysterectomy for symptomatic uterine leiomyomata, abnormal uterine bleeding refractory to hormonal treatment, or both. Patients were randomly assigned to receive a total or supracervical hysterectomy performed using the surgeon's customary technique. Using an intention-to-treat approach, we compared surgical complications and clinical outcomes for 2 years after randomization. Results Sixty-eight participants were assigned to supracervical hysterectomy (SCH) and 67 to total abdominal hysterectomy (TAH). Hysterectomy by either technique led to statistically significant reductions in most symptoms, including pelvic pain or pressure, back pain, urinary incontinence, and voiding dysfunction. Patients randomly assigned to (SCH) tended to have more hospital readmissions than those randomized to TAH, but this difference was not statistically significant. There were no statistically significant differences in the rate of complications, degree of symptom improvement, or activity limitation. Participants weighing more than 100 kg at study entry were twice as likely to be readmitted to the hospital during the 2-year follow-up period (relative risk [RR] 2.18, 95% confidence interval [CI] 1.06, 4.48, P = .034). Conclusion We found no statistically significant differences between (SCH) and TAH in surgical complications and clinical outcomes during 2 years of follow-up.
Creation of a device that allows for people with spina bifida to practice skills necessary to operate a motor vehicle

People with spina bifida have to take a special abilities test in order to receive a drivers license from the state of Louisiana. The Spina Bifida Association of Greater New Orleans has requested a device to help people with spina bifida prepare for this test. The device tests reaction time using a set of lights (output), a processor and program that measure reaction time and a hand controller similar to the type used in motor vehicles adapted for handicapped people (input). This device allows for the testing of reaction time and the practicing of the test in an attempt to improve reaction time.
Effects of water absorption on physical properties and degree of molecular orientation of poly (ethylene terephthalate)

Poly(ethylene terephthalate) (PET) is known to be a hygroscopic thermoplastic, which absorbs moisture from its environment at a rapid rate. The water absorption characteristics of PET as a function of relative humidity, exposure time, temperature, thickness, and molecular weight are reported here. Results indicate that absorbed moisture has significant influences on the physical properties of PET, leading to large decreases in the glass transition temperature, crystallization temperature, and degree of molecular orientation.
Cell-based high-throughput screens for the discovery of chemotherapeutic agents

Jennifer T. Fox1 1 and Kyungjae Myung1 1 1 Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD Received: April 26 , 2012; Accepted: May 29, 2012; Published: May 29, 2012; Keywords: ATAD5-luciferase, genotoxins, DNA repair mutants, cancer, drug discovery Correspondence: Kyungjae Myung, email: // // Abstract With modern advances in robotics and data processing, high-throughput screening (HTS) is playing an increasingly growing role in the drug discovery process. The ultimate success of HTS depends upon the development of assays that are robust and reproducible in miniaturized formats, have low false-positive rates, and can identify drugs that offer improvements over those currently on the market. One example of such an assay is the ATAD5-luciferase HTS assay, which identified three antioxidants that could kill cancer cells without inducing mutagenesis. Here we discuss the ATAD5-luciferase assay and expand upon the value of HTS in identifying other potential cancer drugs, focusing on cell-based assays that involve DNA damage or repair pathways.
An unusual organelle in Cryptococcus neoformans links luminal pH and capsule biosynthesis

Abstract Cryptococcus neoformans is a basidiomycete that causes deadly infections in the immunocompromised. We previously generated a secretion mutant in this fungus by introducing a mutation in the SAV1 gene, which encodes a homolog of the Sec4/Rab8 subfamily GTPases. Under restrictive conditions there are two notable morphological changes in the sav1 mutant: accumulation of post-Golgi vesicles and the appearance of an unusual organelle, which we term the sav1 body (SB). The SB is an electron-transparent structure 0.2–1 μm in diameter, with vesicles or other membranous structures associated with the perimeter. Surprisingly, the SB was heavily labeled with anti-glucuronoxylomannan (GXM) antibodies, suggesting that it contains a secreted capsule component, GXM. A structure similar to the SB, also labeled by anti-GXM antibodies, was induced in wild type cells treated with the vacuolar-ATPase inhibitor, bafilomycin A1. Bafilomycin A1 and other agents that increase intraluminal pH also inhibited capsule polysaccharide shedding and capsule growth. These studies highlight an unusual organelle observed in C. neoformans with a potential role in polysaccharide synthesis, and a link between luminal pH and GXM biosynthesis.
Nucleoporin Phosphorylation Triggered by the Encephalomyocarditis Virus Leader Protein Is Mediated by Mitogen-Activated Protein Kinases

Cardioviruses disrupt nucleocytoplasmic transport through the activity of their leader (L) protein. We have shown that hyperphosphorylation of nuclear pore proteins (nucleoporins or Nups), including Nup62, Nup153, and Nup214, is central to this L protein function and requires one or more cytosolic kinases. In this study, potential cellular enzymes involved in encephalomyocarditis virus (EMCV) L-directed Nup phosphorylation were screened with a panel of specific, cell-permeating kinase inhibitors. Extracellular signal-regulated receptor kinase (ERK) and p38 mitogen-activated protein kinase inhibitors (U0126 and SB203580) were sufficient to block Nup hyperphosphorylation in EMCV-infected or L-expressing cells. Recombinant L alone, in the absence of infection, triggered activation of ERK and p38, independent of their upstream signaling cascades. Conserved residues within the L zinc finger (Cys19) and acidic domain (Asp48,51,52,55) were essential for this activation and for the phosphorylation of Nups, suggesting that the phenomena are linked. Analysis of the hyperphosphorylated Nup species revealed only phosphoserine and phosphothreonine residues. The sizes of the tryptic phosphopeptides derived from Nup62 were compatible with sites in the Phe/Gly repeat domain which display common consensus sequences for ERK and p38 substrates. The results provide strong evidence that ERK and p38 are the probable effector kinases required for L-dependent inhibition of nuclear trafficking.
High-Capacity Ion Trap Coupled to a Time-of-Flight Mass Spectrometer for Comprehensive Linked Scans with no Scanning Losses.

A high-capacity ion trap coupled to a time-of-flight (TOF) mass spectrometer has been developed to carry out comprehensive linked scan analysis of all stored ions in the ion trap. The approach involves a novel tapered geometry high-capacity ion trap that can store more than 10 6 ions (range 800–4000 m/z) without degrading its performance. Ions are stored and scanned out from the high-capacity ion trap as a function of m/z, collisionally fragmented and analyzed by TOF. Accurate mass analysis is achieved on both the precursor and fragment ions of all species ejected from the ion trap. We demonstrate the approach for comprehensive linked-scan identification of phosphopeptides in mixtures with their corresponding unphosphorylated peptides. © 2010 Elsevier B.V. All rights reserved.
The Brain: Ground Zero in Hepatic Insulin Resistance

Recent studies suggest that elevated levels of circulating branched-chain amino acids (BCAAs; for example, leucine, isoleucine, and valine) are predictors of type 2 diabetes (T2D) and obesity. However, the mechanisms of the association remained unexplained. Therefore, Shin et al. conducted a series of translational experiments to establish the mechanisms of elevated diabetes risks with altered BCAA metabolism. Their new results establish a connection between insulin signaling in the brain, BCAA metabolism in the liver, and T2D pathogenesis. The authors used several models across the translational divide to provide solid evidence that insulin signaling specifically in the brain could regulate metabolism in the liver. Using a rat model, they discovered that insulin signaling in the brain induced liver production of the rate-limiting metabolizing enzyme for BCAAs, branched-chain alpha keto acid dehydrogenase (BCKDH). This observation was consistent in neuronal insulin receptor–deficient mice, suggesting that this observation was not spurious. The livers of men with T2D and obesity were found to have decreased serum levels of BCKDH that correlated with elevated levels of BCAAs. Moreover, macaques that were fed a high-fat diet exhibited elevated BCAAs and decreased liver production of BCKDH. Last, the authors used a genetically manipulated version of the nematode Caenorhabditis elegans that exhibited inhibition of neuronal insulin signaling and observed the altered BCAA metabolism phenotype. The investigators concluded that disrupted insulin signaling in the brain decreases the liver’s ability to metabolize BCAAs and contributes to the clinical observations in patients with T2D and obesity. The study used multiple translational approaches to elegantly demonstrate the importance that insulin signaling in the brain has in peripheral insulin resistance. These results suggest that insulin signaling in the brain may be a new therapeutic target in the fight against the current T2D and obesity epidemics. A. C. Shin et al ., Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism. Cell Metab. 10.1016/j.cmet.2014.09.003 (2014). [[Abstract]][1] [1]: http://www.cell.com/cell-metabolism/abstract/S1550-4131(14)00400-8
Chinese zero pronoun resolution: an unsupervised approach combining ranking and integer linear programming

State-of-the-art approaches to Chinese zero pronoun resolution are supervised, requiring training documents with manually resolved zero pronouns. To eliminate the reliance on annotated data, we propose an unsupervised approach to this task. Underlying our approach is the novel idea of employing a model trained on manually resolved overt pronouns to resolve zero pronouns. Experimental results on the OntoNotes 5.0 corpus are encouraging: our unsupervised model surpasses its supervised counterparts in performance.
Estimating Causal Effects Using Coarsened Treatments as Instruments

Researchers often estimate causal effects in experimental or observational studies after coarsening continuous measures of treatments. In the statistical matching context, in particular, non-discrete interventions are frequently discretized to facilitate pair-stratification using traditional matching approaches for binary treatments. A well-known issue in studying coarsened interventions is that any coarsening induces measurement error that attenuates estimates, while inflating estimator standard errors. While this bias is known, there is yet no standard correction for it. This research note illustrates the error-in-variables structure underlying the use of discrete transformations of non-discrete (or dose) interventions. It also recommends the use of the standard IV estimator to recover an unbiased estimate of the uncoarsened treatment effect. Particular attention is given to the problem of matching with a continuous intervention, which motivates simulations.
The Impact of Participation in the Advanced Placement Program on Students' College Admissions Test Scores

ABSTRACTThe Advanced Placement (AP) program is an educational program that permits high school students to take introductory college-level courses and receive college credit by passing a standardized end-of-course exam. Data were obtained from a statewide database of 2 high school graduating cohorts (N = 90,044). We used a series of propensity score analyses and marginal mean weighting through stratification to examine the impact of the AP program on students' academic achievement as measured by ACT scores. Results indicate that merely enrolling in an AP course produces very little benefit for students. Students who take and pass the AP exam, however, obtain higher ACT scores, even after controlling for a wide variety of academic, socioeconomic, and demographic variables. The authors conclude the article by discussing aspects of the AP program that remain unanswered.
Exercise myopathy of the extensor carpi ulnaris muscle. Report of a case

Treating very young children with spinal deformities is challenging and complex, and it entails risks. The consequences of surgical treatment can be profound, with lifelong implications. The recent focus on "fusionless" surgery and spinal column lengthening strategies, such as growing rod instrumentation and the use of a Vertical Expandable Prosthetic Titanium Rib, illustrate the current understanding of the importance of spinal growth and lung development in infants and young children.
In-Vivo Micron Scale Arthroscopic Imaging of Human Knee Osteoarthritis with Optical Coherence Tomography: Comparison with MRI and Arthroscopy

A clinical need exists for a technology to identify early osteoarthritis. This study performs in vivo human arthroscopic OCT imaging with MRI and arthroscopic comparisons, demonstrating OCT as a promising method for identifying early OA.
A clinical comparison of the antipyretic potency of aspirin and sodium salicylate

In a study on adult patients with cancer and low-grade fevers due to chronic infection, aspirin appeared to be 1.5 times as potent as sodium salicylate as an antipyretic. The difference in potency is probably due to the difference in pKa of the two acids.
Parameters Calculation of Photovoltaic Panel Model Based on Newton-Raphson Method

Some field testing data of important operation points are provided by manufacturers of photovoltaic panels,but it is not enough for the simulation study of photovoltaic power generation system because detailed and acuurate parameters of photovoltaic panel model are required. To calculate the parameters of photovoltaic panel model,a Newton-Raphson method is presented in this paper. All the information needed by the method are the data sheet values usually supplied by manufacturers of photovoltaic panels,in which the data of three special operation points of the panel such as the open-circuit point,the short-circuit point and the maximum-power point,can be found easily. Based on these data,the parameters can be worked out in a few steps of iteration. In order to solve the singularity problem appearing in the inverse matrix of the Jacobian matrix,a technique to modify the algorithm is proposed. Simulation study on a practical photovoltaic panel demonstrates the validity and simplicity of the method proposed.
A Rodent Model for Studying Four Well Defined Toxic Endpoints during Bupivacaine Infusion

An animal model with four well defined endpoints for studying the cardiotoxicity and neurotoxicity of bupivacaine is described. Five male Wistar rats (264-324 g) were anesthetized, tracheostomized and ventilated, and ECG and EEG leads were placed. Femoral arteries and veins were then cannulated. Twenty minutes before bupivacaine infusion, 0.1 mg/kg pancuronium was given intravenously, and anesthesia was adjusted to halothane 0.5%, 30% 02 and 70% N20. Bupivacaine infusion was then begun at 2 mg/kg/minute. Bupivacaine doses producing the following endpoints were then determined: (1) first ventricular arrhythmia (ARR), (2) seizures (SZ), (3) isoelectric EEG (ISO EEG), and (4) asystole (ASYS). The doses of bupivacaine (in mg/kg ± SD) precipitating ARR, SZ, ISO EEG and ASYS were 4.22 ± 1.87, 7.08 ± 1.55, 11.05 ± 5.15 and 20.4 ± 6.49 mg/kg, respectively. These endpoints were present and readily determined in all animals. The doses of bupivacaine producing ARR and SZ were not significantly different (p > 0.05). The doses producing SZ, ISO EEG and ASYS were significantly different from each other ( p > 0.05, ANOVA and the Duncan test). These results indicate that it is possible to study, in the anesthetized and paralyzed rat that is intensely monitored, many of the variables associated with local anesthetic toxicity currently of clinical interest. The use of a constant local anesthetic infusion allows ready observation of the progression of toxic signs.
Electrophysiologic effects of intravenous aminophylline in heart transplant recipients with sinus node dysfunction.

Background : Sinus node dysfunction has been reported to occur in up to 50% of orthotopic heart transplant recipients, and oral theophylline has been used in an attempt to limit the morbidity associated with this abnormality. The purpose of this study was to evaluate the electrophysiologic effects of methylxanthines on sinus node function. Methods : Sinus node testing was performed in 26 patients before and after the infusion of 6 mg/kg of aminophylline. Thirteen of these patients had abnormal sinus node function at baseline, and thirteen had normal sinus node function. Sinus node dysfunction was diagnosed by a rhythm other than sinus in five patients, a prolonged corrected sinus node recovery time in two patients, and the presence of a secondary pause in six patients. Results : In patients with abnormal sinus node function a significant decrease was observed in the sinus node recovery time (-14% ± 5%) and corrected sinus node recovery time (- 33% ± 25%) in response to aminophylline ; however, neither parameter was normalized. A decrease in the sinus cycle length (- 6% ± 8%) was not statistically significant. In patients with normal sinus node function, a significant decrease was seen in both the sinus node recovery time (- 9% ± 7%) and sinus cycle length (-9% ± 4%). The corrected sinus node recovery time decreased by 4% ± 28% in patients with normal conditions but was not significant. Overall, aminophylline resolved the underlying sinus node abnormality in only one of thirteen patients with abnormal sinus node function. Conclusions : This study suggests that the use of theophylline in patients with marked sinus node dysfunction may not decrease their risks for subsequent bradycardic events. J HEART LUNG TRANSPLANT 1995 ;14 :429-35.
Ionic Requirements of Transepithelial Potentials in Isolated Cell Layers of Hydra

Because hydra is one of the few fresh water coelenterates, it requires a unique system to maintain ionic and osmotic equilibrium. Several studies in the past have begun to elucidate the mechanism of ionic and osmotic regulation in hydra (Josephson and Macklin, 1969; Macklin, 1967; Macklin and Josephson, 1971; Marshall, 1969). These studies have demonstrated that there is a maintained electrical potential across the hydra epithelium with the gut positive relative to the external medium and it was shown by Macklin and Josephson (1971) that this sustained positive potential was related to an active sodium transport mechanism. Further, superimposed on this sustained positive potential, there are negative going spikes termed “contraction pulses” (CPs) which had been shown to relate to contraction of the body column (Josephson, 1967). Various studies of the osmotic properties of hydra cells and tissue (Benos and Prusch, 1972; Koblick and Yu-Tu, 1967; Lilley, 1955; Marshall, 1969; Steinbach, 1963), have demonstrated that hydra tissue is isosmotic to a solution with an osmotic strength of 40 to 60 milliosmol, and that the gut of the animal is approximately isosmotic to the hydra tissue. These experimental results have led to the conclusion that ionic and osmotic regulation of the intact hydra is maintained by an active transport of sodium with passive movement of water and an anion and with isosmotic flow from the tissue into the gut.
Extended phase I study of AS1411 in renal and non-small cell lung cancers

13098 Background: AS1411 is an oligonucleotide aptamer that binds to nucleolin, a protein expressed on the surface of tumor cells. A dose-escalating phase I trial in patients with various advanced ...