cssi/SciSciGPT-SciSciNet huggingface dataset:
Remote site control of an active site fidelity checkpoint in a viral RNA-dependent RNA polymerase.

The kinetic, thermodynamic, and structural basis for fidelity of nucleicacid polymerases remains controversial. An understanding of viralRNA-dependent RNA polymerase (RdRp) fidelity has become a topic ofconsiderable interest as a result of recent experiments that show that a2-fold increase in fidelity attenuates viral pathogenesis and a 2-folddecrease in fidelity reduces viral fitness. Here we show that a conformationalchange step preceding phosphoryl transfer is a key fidelity checkpoint for thepoliovirus RdRp (3Dpol). We provide evidence that thisconformational change step is orientation of the triphosphate into aconformation suitable for catalysis, suggesting a kinetic and structural modelfor RdRp fidelity that can be extrapolated to other classes of nucleic acidpolymerases. Finally, we show that a site remote from the catalytic center cancontrol this checkpoint, which occurs at the active site. Importantly, similarconnections between a remote site and the active site exist in a wide varietyof viral RdRps. The capacity for sites remote from the catalytic center toalter fidelity suggests new possibilities for targeting the viral RdRp forantiviral drug development.
21.1: Invited Paper: CG Silicon Technology and Development of System on Panel

With CG Silicon technology, the mobile display pertinent to the ubiquitous network era is developed, and provided towards the whole world. Expansion of future CG Silicon applications is explained, and which are high-value-added system liquid crystal display, the high resolution display, audio-visual display and the advanced functional circuit integrated display are introduced.
The role of curvature in entanglement

Abstract Which tangles more readily: curly hair or straight hair? A perhaps natural thought, supported by some theoretical evidence, is to associate curvature and entanglement, and assume that they would grow together—that an increase in one fosters an increase in the other. However we have biological examples such as DNA in the chromosome, and mechanical examples such as coiled telephone cords, in which much more curvature is employed than is required for the packing, and in which tangling is presumably detrimental. We offer a resolution to this conundrum. We show, that at least for simple but generally applicable models, the relationship between curvature and entanglement is subtle: if we keep filament density constant and increase curvature, the entanglement initially increases, passes through a maximum, then decreases, so there is a regime where increasing curvature increases entanglement, and there is also a regime where increasing curvature decreases entanglement. This has implications for filament packing in many circumstances, and in particular for the compaction structure of DNA in the cell—it provides a straightforward argument for the view that one purpose of DNA coiling and supercoiling is to inhibit entanglement. It also tells us to expect that wavy hair–neither the straightest nor the curliest–tangles most readily.
Presentation of reversible posterior leukoencephalopathy syndrome in patients on calcineurin inhibitors.

Abstract Background Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinico-radiologic diagnosis associated with numerous medical conditions including hypertension, immunosuppressant medications, and eclampsia. It is characterized by headache, altered mental status, seizures, visual disturbance, and neuroimaging consistent with posterior-predominant vasogenic edema. The objective of this study was to characterize the clinical spectrum and outcomes in a large series of RPLS patients, and to compare the presentation of patients taking calcineurin inhibitors (CNIs) to that of other RPLS patients. Methods We reviewed records of patients seen by the neurology and transplant services over an 18-year period. Comorbid conditions, medications, blood pressure, laboratory testing, clinical outcomes, and radiographic findings were collected. Results 84 episodes of RPLS were identified in 79 patients. Etiologies included CNIs (43%), hypertension (29%), renal disease (12%), preeclampsia/eclampsia (7%), and chemotherapy (5%). Patients on CNIs had lower blood pressures ( p = 0.002) and a lower prevalence of headache ( p = 0.02) compared to RPLS patients with other etiologies. Clinical recovery occurred in 65% of episodes, and radiographic resolution occurred in 67%. Conclusions Patients with CNI-induced RPLS have lower blood pressure than other RPLS patients, but otherwise present similarly. RPLS typically occurs within days to weeks of CNI initiation in patients without elevated medication levels. Clinical and radiographic recovery occurred in the majority of patients in this series, but one-third suffered residual neurologic deficits or death. These findings highlight the importance of prompt recognition and treatment of RPLS triggers to prevent permanent sequelae.
A simple inexpensive, hydraulic microdrive for recording neocortical unit activity in the unanesthetized rat.

Abstract An inexpensive, hydraulic microdrive is described for recording single unit activity in unanesthetized, unrestrained rats.
New scheme of coherent array detection to cancel out phase fluctuations and Doppler frequency shift due to atmospheric turbulence and target movement for laser communications

A coherent array detection system, which uses multiple independent apertures/receivers whose IFs are electro- optically co-phased in real time and then added together, can mitigate the laser signal fluctuations and fading due to atmospheric turbulence for laser communications and radar. Thus the system performance greatly depends on the electo- optic phase-locked loops (EOPLL) used for the real time co- phase of signals from the independent aperture/receivers. But if the fast phase fluctuations due to atmospheric turbulence or a high Doppler frequency shift due to the target (satellite) movement are induced to the laser signal which is beyond the response speed of the EOPLL, the system can not mitigate the signal fluctuations and fading anymore. This paper presents a new scheme which can make the coherent array detection system get rid of the EOPLL. This scheme uses a reference laser beam as well as laser signal with different polarization as the transmitted beam. By separating the received laser reference beam and signal due to their polarization and through two stage mixing, the IF signals from the multiple independent aperture/receivers will be co-phased automatically.
Postmortem interrogation and retrieval of implantable pacemakers and defibrillators: a survey of morticians and patients.

Device Retrieval Survey of Morticians and Patients. Introduction: Recent recalls of pacemakers and defibrillators cast a spotlight on product reliability. Universal postmortem device analysis could yield valuable information, but little data exist on the rate and feasibility of device examinations following death. This study investigated how morticians manage pacemakers and defibrillators and surveyed morticians and device patients regarding routine postmortem device interrogation and explantation. Methods and Results: Seventy-one morticians were surveyed on device interrogation and explantation practices. One hundred fifty patients presenting for routine device interrogation were interviewed regarding preferences for what should be done with devices postmortem and willingness to execute “device advance directives” authorizing analysis and retrieval. The average number of devices annually explanted per mortician was 7 ± 10 (range = 1 to 50). The most common methods of disposal were placement in medical waste (44%) and donation for human reimplantation in developing nations (18%). Only 4% of morticians reported ever returning devices to manufacturers, but 87% agreed that routine explantation and return of devices to manufacturers would be feasible. Eighty-seven percent of device patients had no understanding of how their device would be handled after death. However, a majority (82%) indicated a willingness to have their device interrogated after death, and most (79%) were willing to have it returned to manufacturers. Willingness was not associated with age, sex, time since device implantation, or device type. Conclusions: Implantable pacemakers and defibrillators are rarely analyzed after patients die. Systematic postmortem device retrieval appears feasible and acceptable to morticians and patients. Further efforts are needed to implement universal postmortem device evaluation. (J Cardiovasc Electrophysiol, Vol. 18, pp.
Why are maximizers less happy than satisficers? Because they maximize positive and negative outcomes

Although extant research suggests maximizing is related to objectively positive outcomes (e.g., job offers), I propose maximizing may be simultaneously and positively related to objectively negative outcomes (e.g., job rejections). Specifically, I argue maximizers bear more instances of positive and negative outcomes than satisficers, and that in spite of their positive outcomes—yet because of their negative outcomes—maximizers are less happy than satisficers. In Study 1, participants took the alternate uses test; as expected, maximizing was related to seeking alternatives, yet, maximizing was also related to seeking low-quality alternatives. Moreover, the number of low-quality alternatives partially mediated the relationship between maximizing and negative affect. In Study 2, the impact of maximizing on experiencing negative affect was further assessed by examining whether maximizing is related to seeking and choosing low-quality alternatives. Participants played the Iowa Gambling Task; it was found maximizing was related to alternating among decks, and in particular, sampling bad decks; ultimately, maximizing was related to winning less money, and experiencing more negative affect. Finally, in Study 3, participants responded to questionnaires about positive and negative life outcomes; it was found that maximizing was simultaneously related to experiencing more positive and more negative outcomes, and that negative outcomes predicted happiness to a greater degree than positive outcomes. These findings suggest an irony of maximizing: It produces both positive and negative outcomes, contributing to literature explaining why maximizers are less happy than satisficers, and ultimately whether happiness is a matter of choice. Copyright © 2009 John Wiley & Sons, Ltd.
A self-driven laser oscillator for directly producing bandwidth-limited pulses of about 1 nsec

Abstract We report a self-driven Nd:YAG oscillator system that directly produces bandwidth-limited output pulses with durations from
Spectral Radiance of Sky and Terrain at Wavelengths between 1 and 20 μ. III. Terrain Measurements

A mobile infrared spectrographic laboratory has been used to make absolute determinations of the apparent infrared spectral radiance of various types of terrain. The spectral distribution of the observed radiation indicates the predominance of reflected sun and sky radiation at wavelengths less than approximately 3 μ, and thermal emission at longer wavelengths. Examples are shown for a number of types of terrain observed in various locations and conditions. The transition between the sky and the ground is also illustrated by spectra taken near the horizon. The spectra of gypsum and silica sands show reststrahlen effects in the atmospheric window of wavelengths between 8 and 13 μ. Many of the features of the spectra of terrain can be explained, in some cases quantitatively, on the basis of known parameters of the particular background and its atmospheric environment.
Attachment of adeno-associated virus type 3H to fibroblast growth factor receptor 1.

Heparan sulfate proteoglycan is thought to act as primary receptor for adeno-associated virus type 2 (AAV-2). Reported coreceptors include αVβ5 integrin, fibroblast growth factor receptor 1 (FGFR-1), and hepatocyte growth factor (c-Met). The interaction of AAV type 3 (AAV-3) with possible cell membrane receptors is incompletely defined. In this study, using assays detecting competition with viral infection, virus binding inhibition assays and dot blotting, we show attachment of AAV-3 strain H to heparin, heparan sulfate, and FGFR-1. These findings provide new information on the possible receptor array used by AAV-3.
Establishing HIV treatment as prevention in the HIV Prevention Trials Network 052 randomized trial: an ethical odyssey

Background Obtaining the definitive data necessary to determine the safety and efficacy of using antiretroviral treatment (ART) to reduce the sexual transmission of HIV in heterosexual couples encountered an array of ethical challenges that threatened to compromise HIV Prevention Trials Network (HPTN) 052, the multinational clinical trial addressing this issue that has profound public health implications.Purpose To describe and analyze the major ethical challenges faced in HPTN 052.Methods The ethical issues and modifications of HPTN 052 in response to these issues were cataloged by the principal investigator, the lead coordinator, and the ethicist working on the trial. The major ethical issues that were unique to the trial were then described and analyzed in light of the published literature as well as guidances and policies. The ethical challenges that must be addressed in many clinical trials, such as those related to obtaining informed consent and making provisions for ancillary care, are not describe...
QUANTITATIVE CHEMICAL STUDIES ON COMPLEMENT OR ALEXIN : III. UPTAKE OF COMPLEMENT NITROGEN UNDER VARYING EXPERIMENTAL CONDITIONS.

1. Quantitative data are given on the effect of variations in the time of contact and the proportions of the reactants on the quantity of complement combining component nitrogen (C'1 N) found in active guinea pig serum. 2. C'1 N was the same when determined with precipitates containing excess antibody or excess antigen. 3. Finely divided specific precipitates took up the complement combining component (C'1) from subsequently added guinea pig serum almost as well as specific precipitates formed in the presence of complement.
The Sodium/Proton Exchanger Nhx1p Is Required for Endosomal Protein Trafficking in the Yeast Saccharomyces cerevisiae

We show that the vacuolar protein sorting gene VPS44 is identical to NHX1, a gene that encodes a sodium/proton exchanger. The Saccharomyces cerevisiae protein Nhx1p shows high homology to mammalian sodium/proton exchangers of the NHE family. Nhx1p is thought to transport sodium ions into the prevacuole compartment in exchange for protons. Pulse-chase experiments show that ;35% of the newly synthesized soluble vacuolar protein carboxypeptidase Y is missorted in nhx1D cells, and is secreted from the cell. nhx1D cells accumulate late Golgi, prevacuole, and lysosome markers in an aberrant structure next to the vacuole, and late Golgi proteins are proteolytically cleaved more rapidly than in wild-type cells. Our results show that efficient transport out of the prevacuolar compartment requires Nhx1p, and that nhx1D cells exhibit phenotypes characteristic of the “class E” group of vps mutants. In addition, we show that Nhx1p is required for protein trafficking even in the absence of the vacuolar ATPase. Our analysis of Nhx1p provides the first evidence that a sodium/proton exchange protein is important for correct protein sorting, and that intraorganellar ion balance may be important for endosomal function in yeast.
Quaker dress, sexuality, and the domestication of reform in the Victorian novel.

WHY ARE JANE EYRE AND DOROTHEA BROOKE clad by their creators in “Quakerish” garb? The oppositional plainness and simplicity of Quakerish heroines have often been read as signs of classlessness and sexlessness.1 Plain and simple clothing seems, to both Victorian and contemporary eyes, part of the package of reticence, reserve, and repression associated with the evangelical wing of nineteenth-century dissenting sects.2 The typical sociological view of the function of dress within conservative religious groups holds that “strict dress codes are enforced because dress is considered symbolic of religiosity. Hence dress becomes a symbol of social control as it controls the external body” (Arthur 1). The control of female sexuality and the restraint of desire would seem to be the core function of modest clothing. Then the plain dress of some of the liveliest heroines of Victorian fiction presents a puzzle that can be solved only by recuperating the meaning of that clothing for Victorians. As fashion historian Anne Hollander points out, nineteenth-century novels testify to the way that clothes “always correctly express character” (Feeding the Eye 12), but the meaning of particular articles of clothing or styles can slip away. Accurately reading the characters of Charlotte Bronte and George Eliot thus requires careful interpretation of their dress, in this case reversing the conventional reading of their plain, modest, and simple style. This essay argues that Quakerish clothing expresses both a promise of spirited sexuality and an admonition about the class-crossing potential of the respectable female contained within it.
An investigation of individual recognition by voice in female red-winged blackbirds

Abstract In order to determine if female Red-winged Blackbirds (Agelaius phoeniceus) recognize each other as individuals on the basis of voice alone, playback experiments with 31 resident female redwings were performed. Female redwings sing two distinct song types. Fifteen females were exposed to Type 1 neighbour and Type 1 non-neighbour songs, and 16 females were exposed to Type 2 neighbour and Type 2 non-neighbour songs. Based on matched-pairs comparisons of the females' behavioural responses to the playback songs, female redwings do not appear to distinguish each other individually by voice. Loudspeaker placeement may be one confounding variable of significant importance in auditory individual recognition experiments.
The Sm‐like protein Hfq regulates polyadenylation dependent mRNA decay in Escherichia coli

In Escherichia coli, the post-transcriptional addition of poly(A) tails by poly(A) polymerase I (PAP I, pcnB) plays a significant role in cellular RNA metabolism. However, many important features of this system, including its regulation and the selection of polyadenylation sites, are still poorly understood. Here we show that the inactivation of Hfq (hfq), an abundant RNA-binding protein, leads to the reduction in the ability of PAP I to add poly(A) tails at the 3' termini of mRNAs containing Rho-independent transcription terminators even though PAP I protein levels remain unchanged. Those poly(A) tails that are synthesized in the absence of Hfq are shorter in length, even in the absence of polynucleotide phosphorylase (PNPase), RNase II and RNase E. In fact, the biosynthetic activity of PNPase in the hfq single mutant is enhanced and it becomes the primary polynucleotide polymerase, adding heteropolymeric tails almost exclusively to 3' truncated mRNAs. Surprisingly, both PNPase and Hfq co-purified with His-tagged PAP I under native conditions indicating a potential complex among these proteins. Immunoprecipitation experiments using PNPase- and Hfq-specific antibodies confirmed the protein-protein interactions among PAP I, PNPase and Hfq. Analysis of mRNA half-lives in hfq, deltapcnB and hfq deltapcnB mutants suggests that Hfq and PAP I function in the same mRNA decay pathway.
"Summary Page": A Novel Tool That Reduces Omitted Data in Research Databases

Data entry errors are common in clinical research databases. Omitted data are of particular concern because they are more common than erroneously inserted data and therefore could potentially affect research findings. However, few affordable strategies for their prevention are available. We have conducted a prospective observational study of the effect of a novel tool called "Summary Page" on the frequency of correction of omitted data errors in a radiation oncology research database between July 2008 and March 2009. "Summary Page" was implemented as an optionally accessed screen in the database that visually integrates key fields in the record. We assessed the frequency of omitted data on the example of the Date of Relapse field. We considered the data in this field to be omitted for all records that had empty Date of Relapse field and evidence of relapse elsewhere in the record. A total of 1,156 records were updated and 200 new records were entered in the database over the study period. "Summary Page" was accessed for 44% of all updated records and for 69% of newly entered records. Frequency of correction of the omitted date of cancer relapse was six-fold higher in records for which "Summary Page" was accessed (p = 0.0003). "Summary Page" was strongly associated with an increased frequency of correction of omitted data errors. Further, controlled, studies are needed to confirm this finding and elucidate its mechanism of action.
"Probable" versus "confirmed" leptospirosis: an epidemiologic and clinical comparison utilizing a surveillance case classification.

Abstract PURPOSE: For surveillance purposes, the Centers for Disease Control and Prevention and Council of State and Territorial Epidemiologists (CDC/CSTE) have defined two case classifications for leptospirosis: “confirmed” and “probable.” The objective of this study was to provide data to refine the current surveillance case classifications. METHODS: All reported leptospirosis infections from exposures within the State of Hawaii, 1974 to 1998 meeting CDC/CSTE “confirmed” and “probable” case classifications were compared on a number of clinical and epidemiologic parameters. RESULTS: Confirmed cases (n = 276) had more severe clinical manifestations than probable cases (n = 180); however, probable cases with higher peak microscopic agglutination test (MAT) titers (⩾1:800) were clinically and epidemiologically comparable to confirmed cases. In addition, 77 cases demonstrating fourfold or greater MAT titer increases in paired serum collected less than two weeks apart (currently excluded from the “confirmed” case classification) were also comparable to confirmed cases. CONCLUSIONS: Our findings support amending the current CDC/CSTE surveillance confirmed case classification to include demonstration of a fourfold or greater MAT titer increase in paired serum, irrespective of the interval between specimen collection. Consideration should also be given to including single MAT titer ⩾1:800 as a criterion for “confirmation.” These changes would both simplify and expedite the surveillance confirmation of leptospirosis.
Irreducibility of some Faber polynomials

Apply weight 0 Hecke operators to the modular function j and express the result as a polynomial in j. These polynomials were considered long ago in analysis, and recently attracted the attention of number theorists primarily for their connection with Borcherds’ infinite products. In particular, Ken Ono conjectured that all of them are irreducible. We prove a partial result towards this conjecture by presenting infinite families of these polynomials which are proved to be irreducible.
Neuronal responses to target onset in oculomotor and somatomotor parietal circuits differ markedly in a choice task

We often look at and sometimes reach for visible targets. Looking at a target is fast and relatively easy. By comparison, reaching for an object is slower and is associated with a larger cost. We hypothesized that, as a result of these differences, abrupt visual onsets may drive the circuits involved in saccade planning more directly and with less intermediate regulation than the circuits involved in reach planning. To test this hypothesis, we recorded discharge activity of neurons in the parietal oculomotor system (area LIP) and in the parietal somatomotor system (area PRR) while monkeys performed a visually guided movement task and a choice task. We found that in the visually guided movement task LIP neurons show a prominent transient response to target onset. PRR neurons also show a transient response, although this response is reduced in amplitude, is delayed, and has a slower rise time compared with LIP. A more striking difference is observed in the choice task. The transient response of PRR neurons is almost completely abolished and replaced with a slow buildup of activity, while the LIP response is merely delayed and reduced in amplitude. Our findings suggest that the oculomotor system is more closely and obligatorily coupled to the visual system, whereas the somatomotor system operates in a more discriminating manner.
Perioperative Management of DORV.

The diagnosis of double-outlet right ventricle (DORV) characterizes a complex heterogeneous group of congenital cardiac malformations for which multiple classification schemes have been used. A clear understanding of the anatomy is critical to understanding the physiologic consequences of the specific type of DORV. Perioperative considerations include the medical management of the patient during the preoperative period, anesthetic and surgical management, and postoperative care. Both anesthetic and surgical management strategies are very different depending on the type of DORV. Key principles for anesthetic management include balancing the systemic and pulmonary circulations, optimizing systemic cardiac output, and closely monitoring for impaired oxygen delivery to the tissues. Depending on the specific anatomy the patient is usually placed on a 1- or 2-ventricle pathway, and initial palliation may involve placement of a systemic arterial to pulmonary artery shunt or pulmonary artery banding. In some cases the child may undergo a complete repair during the first few months of life. Surgical outcomes, both short and long-term, are dependent on the type of DORV and surgical procedure done. These patients require long-term follow up and may present for surgical or catheter-based interventions as adults.
Effects of yeast-derived beta-glucans on blood cholesterol and macrophage functionality

The objective of this study is to investigate the effects of two different yeast-derived beta-glucans on macrophage functionality and blood cholesterol levels in mice. After establishing their ability to act as a strong stimulator of macrophages, we measured the capacities of the glucans to lower blood cholesterol. Our results showed that consumption of diets containing yeast-derived beta-glucan indicated a dose-dependent decrease in plasma cholesterol levels, with Betamune having a significantly stronger effect than WGP (Whole Glucan Particles). In hypercholesterolemic subjects, the cholesterol- and triglycerides-lowering effects of Betamune were again significantly stronger. The results of this investigation demonstrated that highly purified yeast-derived beta-glucans modify plasma cholesterol levels and other indicators associated with artherogenic progression in mice. The fact that these glucans also strongly stimulated both monocytes and macrophages supports the hypothesis that there could be a macrophage-cholesterol (metabolism) axis involvement in these outcomes.
PRELIMINARY ANALYSIS OF THE PEAKS OF STRONG EARTHQUAKE GROUND MOTION--DEPENDENCE OF PEAKS ON EARTHQUAKE MAGNITUDE, EPICENTRAL DISTANCE, AND RECORDING SITE CONDITIONS

Analyses of peak amplitudes of strong earthquake ground motion have been carried out with the emphasis on their dependence on earthquake magnitude, epicentral distance, and geological conditions at the recording site. Approximate empirical scaling functions have been developed which, for a selected confidence level, yield an estimate of an upper bound of peak accelerations, velocities, and displacements. The parameters in these scaling functions have been computed by least-squares fitting of the recorded data on peak amplitudes which are now available for a range of epicentral distances between about 20 and 200 km and are representative for the period from 1933 to 1971 in the Western United States. The possibility of extrapolating the derived scaling laws to small epicentral distances where no strong-motion data are currently available has been tested by comparing predicted peak amplitudes with related parameters at the earthquake source. These source parameters (average dislocation and stress drop) can be derived from other independent studies and do not contradict the inferences presented in this paper. It has been found that for an approximate 90 per cent confidence level the presently available data suggest that peak accelerations, velocities, and displacements at the fault and for the frequency band between 0.07 and 25 Hz probably do not exceed about 3 to 5 g, 400 to 700 cm/sec, and 200 to 400 cm, respectively. The logarithms of the peaks of strong ground motion seem to depend in a linear manner on earthquake magnitude only for small shocks. For large magnitudes this dependence disappears gradually and maximum amplitudes may be achieved for M ≈ 7.5. The influence of geological conditions at the recording site appears to be insignificant for peak accelerations but becomes progressively more important for peaks of strong-motion velocity and displacement.
A complete second-order theory for the unsteady flow about an airfoil due to a periodic gust

A uniformly valid second-order theory is developed for calculating the unsteady incompressible flow that occurs when an airfoil is subjected to a convected sinusoidal gust. Explicit formulas for the airfoil response functions (i.e., fluctuating lift) are given. The theory accounts for the effect of the distortion of the gust by the steady-state potential flow around the airfoil, and this effect is found to have an important influence on the response functions. A number of results relevant to the general theory of the scattering of vorticity waves by solid objects are also presented.
Classification methods for the development of genomic signatures from high-dimensional data

Personalized medicine is defined by the use of genomic signatures of patients to assign effective therapies. We present Classification by Ensembles from Random Partitions (CERP) for class prediction and apply CERP to genomic data on leukemia patients and to genomic data with several clinical variables on breast cancer patients. CERP performs consistently well compared to the other classification algorithms. The predictive accuracy can be improved by adding some relevant clinical/histopathological measurements to the genomic data.
Cost-effectiveness and evidence evaluation as criteria for coverage policy.

ABSTRACT: Private health plans and government health insurance programs in the United States base their coverage decisions on evidence criteria, rather than explicit cost-effectiveness criteria. As...
Antiviral Stilbene 1,2-Diamines Prevent Initiation of Hepatitis C Virus RNA Replication at the Outset of Infection

The recent development of a cell culture model of hepatitis C virus (HCV) infection based on the JFH-1 molecular clone has enabled discovery of new antiviral agents. Using a cell-based colorimetric screening assay to interrogate a 1,200-compound chemical library for anti-HCV activity, we identified a family of 1,2-diamines derived from trans-stilbene oxide that prevent HCV infection at nontoxic, low micromolar concentrations in cell culture. Structure-activity relationship analysis of ~ 300 derivatives synthesized using click chemistry yielded compounds with greatly enhanced low nanomolar potency and a > 1,000:1 therapeutic ratio. Using surrogate models of HCV infection, we showed that the compounds selectively block the initiation of replication of incoming HCV RNA but have no impact on viral entry, primary translation, or ongoing HCV RNA replication, nor do they suppress persistent HCV infection. Selection of an escape variant revealed that NS5A is directly or indirectly targeted by this compound. In summary, we have identified a family of HCV inhibitors that target a critical step in the establishment of HCV infection in which NS5A translated de novo from an incoming genomic HCV RNA template is required to initiate the replication of this important human pathogen.
Black Ants and Buddhism: Second Graders Use Classroom Conflict to Explore World Religions

One day during snack, a conflict exploded in my second grade class when a girl screamed that there were black ants under her chair, and several classmates rushed over to stomp on them. Som-Jet, a s...
Solvent processible, high-performance partially fluorinated copoly (arylene ether) alkaline ionomers for alkaline electrodes

Alkaline ionomers Alkaline electrodes Fuel cells Water uptake Ionic conductivity a b s t r a c t A solvent processable, low water uptake, partially fluorinated copoly(arylene ether) functionalized with pendant quaternary ammonium groups (QAPAE) was synthesized and uses as the ionomer in alkaline electrodes on fuel cells. The quaternized polymers containing fluorinated biphenyl groups were synthesized via chloromethylation of copoly(arylene ether) followed by amination with trimethylamine. The resulting ionomers were very soluble in polar, aprotic solvents. Highly aminated ionomers had conductivities approaching 10 mS cm−1 at room temperature. Compared to previous ionomers based on quaternized poly(arylene ether sulfone) (QAPSF) with similar ion exchange capacity (IEC), the water uptake of QAPAE was significantly less due to the hydrophobic octafluoro-biphenyl groups in the backbone. The performance of the fuel cell electrodes made with the QAPAE ionomers was evaluated as the cathode on a hybrid AEM/PEM fuel cell. The QAPAE alkaline ionomer electrode with IEC = 1.22 meq g −1 had superior performance to the electrodes prepared with QAPSF, IEC = 1.21 meq g−1 at 25 and 60 ◦C in a H2/O2 fuel cell. The peak power densities at 60 ◦ C were 315 mW cm −2 for QAPAE electrodes and
Activity and kinematics of members of the TW Hydrae association

We present high-resolution echelle spectroscopy of 20 stars in 16 systems catalogued as members of the TW Hydrae association, and 16 stars identified as possible new members. We have calibrated the range of coronal and chromospheric activity expected for such young stars as a function of spectral type by combining our observations with literature data for field and open cluster stars. We also compute space motions for TWA members and candidate members with proper motion measurements, using two techniques to estimate distances to stars lacking direct trigonometric parallax measurements. The mean space motion of the four TWA members with known parallaxes is (U, V, W; -10.0, -17.8, -4.6) km s - 1 . 14 of the candidates have properties inconsistent with cluster membership; the remaining two are potential new members, although further observations are required to confirm this possibility.
A Survey-Based Procedure for Measuring Uncertainty or Heterogeneous Preferences in Markets, with Application to a New Test for Common Values

The effects of heterogeneous preferences or uncertainty about item values on the variance of dependent variables (e.g., auction prices; retail price dispersion; or investment choices in stocks, R&D, or education) are usually relegated to the error term, which a) confounds these effects with other drivers of the error term and b) could lead to heteroskedasticity at best or omitted variable bias at worst. This paper shows how surveys can generate a measure of the amount of information or heterogeneity of preferences in a market by measuring the distribution of private information signals in eBay online auctions for computers. Regressions utlizing this measure produce significantly different results than those that rely on hedonic measures to control for heterogeneity alone. Furthermore, this measure provides a new way to test for the presence of a common values component in auctions.
Effect of "Green" (LEED and ENERGY STAR) Designation on Prices/sf and Transaction Frequency: The Chicago Office Market

Executive Summary. This is an empirical study of the economics of green (LEED and ENERGY STAR) designation among all downtown Chicago office transactions spanning 12 years. Green properties achieve...
Rico, Judicial Activism, and the Roots of Separation of Powers

This article demonstrates how, by recalling that separation of power rests on down-to-earth realities of human nature, the offensiveness of judicial activism becomes clear. No longer cloaked in abstraction, such activism displays the bias, prejudice, and arrogance that the Framers sought to check. The injury is only magnified when the judicial revision is to a powerful statute like the Racketeering Influenced Corrupt Organization Act (RICO) - the litigation equivalent to a ballistic missile attack. One side of the split of authority explored here demonstrates a flagrant misreading of civil RICO statutes by certain courts who act as if they were legislators. The thesis here is that separation of powers has come to be discussed as an end itself, rather than as a means to achieve the principles the Framers valued. It is hard for judges to get too embarrassed about violating a political theory. Tell them that judicial revision of a statute is per se ambitious and arrogant conduct, and maybe they are less inclined to improvise - at least in dealing with statutes. We have forgotten that the primary basis for the "controuls" Madison and others placed in our Constitution was to limit the weaknesses of human beings as individuals and to promote the virtues of people working in a system. By renewing the focus on the principles underlying separation of powers, we will force courts to recognize that their role in our system - though important - is limited.
Chiari Malformations and Syringohydromyelia in Children

Chiari malformations are a heterogeneous group of disorders with distinct clinical anatomical features all of which involve the hindbrain. Our understanding of Chiari malformations increased tremendously over the past decades, and progress in neuroimaging was instrumental for that. Conventional and advanced neuroimaging of the brain and spine play a key role in the workup of children with suspected Chiari malformations. In addition, neuroimaging studies in Chiari malformations may guide the management, serve as a predictor of outcome, and shed light on the pathogenesis.
Measurement of ablative Richtmyer-Meshkov growth in planar geometry

Inertial confinement fusion requires the passage of multiple shocks through the plastic ablator of a capsule containing deuterium-tritium (DT) fuel. The shocks cause the capsule to implode with a factor of >35 compression. The ablation process driving these strong shocks, however, causes any mass perturbations on the outside of the capsule to grow due to the ablative Richtmyer-Meshkov instability whose primary role is to seed later time Rayleigh-Taylor. Unstable growth of these perturbations may lead to jetting and mix of cold ablator material into the DT fuel thus hindering ignition. In order to validate design calculations of this effect, experiments at the Omega laser measured the growth of imposed two-dimensional perturbations (bumps) in a CH planar foil. In these experiments, a half Hohlraum is heated by up to 800 J of laser light, creating a radiation temperature of up to 70 eV. The soft x-ray ablation drives a shock into the CH with a velocity measured to be 11 microns/ns. The resulting time evolution of the areal density perturbation, first growing to ∼2× of initial then decreasing as expected from theory, was measured. Simulations of these experiments were found to be in very good agreement with the LEOS 5310 equation of state for CH.
MRI shines (radiofrequency) light on kidney physiology

there is no organ in which structure and function are more directly coupled than in the kidney. Physiological abnormalities in the kidney can be a direct reflection of microstructural pathology, a fact long recognized by clinicians who use biopsy to assess disease state. New technology in small
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Genetics of a contact zone between three chromosomal forms of the grasshopper mouse (Genus Onychomys): a reassessment

Chromosomal, genic, and morphologic data were used to reassess the specific status of Onychomys arenicola relative to O. torridus and O. leucogaster at a previously investigated zone of sympatry (Hinesley, 1979). Chromosomal analysis revealed one karyotypic variant in a sample of 28 individuals of all three taxa. This individual exhibited a fundamental number intermediate between O. torridus and O. arenicola based on non-differentially stained karyotypes, suggesting that it might be an F1 hybrid between the latter two taxa. However, estimates of hybridization between these two taxa based on standard karyotypic methods are unreliable, and the systematic status of O. arenicola cannot be determined using standard karyotypic techniques alone (Hinesley, 1979). Electrophoretic analysis of all three species from the zone of sympatry indicates a lack of genic introgression between the three taxa. The one chromosomal variant was genically indistinguishable from O. torridus . Genie, bacular, and cranial analyses support the specific status of O. arenicola , and indicate a closer phylogenetic relationship between O. leucogaster and O. arenicola , than between O. arenicola and its presumed sister taxon, O. torridus .
Father involvement in Mexican-origin families: Preliminary development of a culturally informed measure.

Objectives An increasing body of research has documented the significant influence of father involvement on children's development and overall well-being. However, extant research has predominately focused on middle-class Caucasian samples with little examination of fathering in ethnic minority and low-income families, particularly during the infancy period. The present study evaluated measures of early father involvement (paternal engagement, accessibility, and responsibility) that were adapted to capture important cultural values relevant to the paternal role in Mexican-origin families. Methods A sample of 180 Mexican-origin mothers (M age = 28.3) and 83 Mexican-origin fathers (M age = 31.5) were interviewed during the perinatal period. Results Descriptive analyses indicated that Mexican-origin fathers are involved in meaningful levels of direct interaction with their infant. A 2-factor model of paternal responsibility was supported by factor analyses, consisting of a behavioral responsibility factor aligned with previous literature and culturally derived positive machismo factor. Qualities of the romantic relationship, cultural orientation, and maternal employment status were related to indices of father involvement. Conclusions These preliminary results contribute to understanding of the transition to fatherhood among low-income Mexican-origin men and bring attention to the demographic, social, and cultural contexts in which varying levels of father involvement may emerge.
Neither Market nor Sate Domain Nonprofits From the Ostroms’ Theoretical Perspective

This article explores the Ostroms’ perspective on nonprofit enterprises and on the place of the “third sector” within the broader ecology of governmental, for-profit, and nonprofit forms of social organization, focusing on three levels: the micro level based on a taxonomical analysis of the nature of (quasi)public goods and of the implications of their heterogeneity for their provision and consumption through nonprofit arrangements (with a special focus on the notion of “coproduction”); the mezzo level—the analysis of the various organizational structures emerging around (quasi)public goods dealt with by compounded units of production, provision, and consumption (with a focus on the notion of “public economy”); and the macro level—the introduction of the notion of “polycentricity” as a meta-framework inviting a reconceptualization of the relationships between the for-profit, nonprofit, and governmental organizations in diverse and dynamic institutional environments.
Blood flow in the various compartments of the goat stomach.

Blood flow rates in the mucosa and muscularis sections of the rumen, reticulum, omasum and abomasum of conscious goats have been measured by using radioactive microspheres. Blood flow rates to the rumen mucosa in ml/100 g tissue/min were 33·56 ±4·5, 11·64 ±3·2 and 7·1·8±1·6 under control conditions and during adrenaline and noradrenaline infusions respectively. The flow to the rumen muscularis under similar conditions were 12·5 ±2·4, 4·08± 1·3 and 3·14 + 0·5. In the fundic mucosa, the blood flow rates were 50·52 ± 5·8, 14·74 ±3·7 and 12·66 ±2·6 while the flow rates to the fundic muscularis were 18·26 ±3·8, 6·62±1·8 and 5·58+1·6. The flow rates to the pyloric mucosa were 31·28±2·8, 4·29±2·2 and 3·84 ±0·5 while the flow rates to the pyloric muscularis were 14·61±2·4, 5·42±1·6 and 4·62+1·9 ml/100 g tissue/min. The blood flow rates to these various sections under control conditions were significantly higher than during adrenaline and noradrenaline infusions (P
Effects of Labeling and Treatment of Hypertension on Perceived Health

The effects of labeling a person as hypertensive have important implications for hypertension screening. The Hypertension Detection and Follow-up Program (HDFP) provides an opportunity to examine the effects of labeling, treatment, and study assignment on a large group of hypertensives (n = 10,070). Their answers to questions regarding perceived health and general well-being asked at baseline and again one year later were analyzed. There was no significant change in the perceived health status of persons who were unaware of their hypertension at baseline and remained untreated at one year (labeling alone). The effect of labeling plus treatment was associated with a significant decrease in perceived health. The effect of antihypertensive drug therapy on perceived health status was examined in persons who were aware of their hypertension but not on treatment at baseline, and on treatment at one year. The stepped care group (SC) had a significant improvement in their perceived health and a significant decrease in the amount of time spent worrying about their health. The referred care group (RC) had no change. Program assignment effects were studied in individuals aware of their hypertension and on treatment both at baseline and one year later. Both the SC and RC groups had a significant improvement in their perceptions of their health status. The SC group had a significant decrease in time spent worrying about their health, while the RC group showed no change. These reassuring results fail to support the suggestion that labeling persons as hypertensive is necessarily followed by negative psychological consequences. They suggest that a supportive system of follow-up may even modestly improve a person’s perception of his or her health status.