cssi/SciSciGPT-SciSciNet huggingface dataset:
Cannabinoid Discrimination and Antagonism by CB 1 Neutral and Inverse Agonist Antagonists

Cannabinoid receptor 1 (CB1) inverse agonists (e.g., rimonabant) have been reported to produce adverse effects including nausea, emesis, and anhedonia that limit their clinical applications. Recent laboratory studies suggest that the effects of CB1 neutral antagonists differ from those of such inverse agonists, raising the possibility of improved clinical utility. However, little is known regarding the antagonist properties of neutral antagonists. In the present studies, the CB1 inverse agonist SR141716A (rimonabant) and the CB1 neutral antagonist AM4113 were compared for their ability to modify CB1 receptor–mediated discriminative stimulus effects in nonhuman primates trained to discriminate the novel CB1 full agonist AM4054. Results indicate that AM4054 serves as an effective CB1 discriminative stimulus, with an onset and time course of action comparable with that of the CB1 agonist Δ9-tetrahydrocannabinol, and that the inverse agonist rimonabant and the neutral antagonist AM4113 produce dose-related rightward shifts in the AM4054 dose-effect curve, indicating that both drugs surmountably antagonize the discriminative stimulus effects of AM4054. Schild analyses further show that rimonabant and AM4113 produce highly similar antagonist effects, as evident in comparable pA2 values (6.9). Taken together with previous studies, the present data suggest that the improved safety profile suggested for CB1 neutral antagonists over inverse agonists is not accompanied by a loss of antagonist action at CB1 receptors.
The PLZF gene of t (11;17)-associated APL.

The PLZF gene is one of five partners fused to the retinoic acid receptor αin acute promyelocytic leukemia. PLZF encodes a DNA-binding transcriptional repressor and the PLZF-RARα fusion protein like other RARα fusions can inhibit the genet program mediated by the wild tpe retinoic acid receptor. However an increasing body of literature indicates an important role for the PLZF gene in growth control and development. This information suggests that loss of PLZF function might also contribute to leukemogenesis.
Meta analysis of the treatment-related factors of external apical root resorption.

Structured Abstract Authors – Segal GR, Schiffman PH, Tuncay OC Objective – To elucidate possible treatment-related etiological factors – such as, duration of treatment and apical displacement – for external root resorption. Design – Meta-analysis of the available English-language literature. Inclusion & Exclusion Criteria – Papers with a sample size >10, fixed appliances, pre- and post-operative radiographs, and apical displacement recorded were included. History of trauma, prior root resorption and endodontic treatment were excluded. Appropriateness of these selections was tested with a ‘funnel plot’ analysis. Outcome Measure – Correlations between root resorption, apical displacement, and treatment duration. Results – Mean apical root resorption was strongly correlated with total apical displacement (r = 0.822) and treatment duration (r = 0.852). Conclusion – The treatment-related causes of root resorption appear to be the total distance the apex had moved and the time it took.
Interactive visualization of quaternion Julia sets

The first half of a two-step quaternion Julia set visualization system is described. This step uses a quarternion square root function to adapt the classic inverse iteration algorithm to the quaternions. The augmented version produces a 3-D Julia set defined by a point cloud that can be interactively manipulated on a graphics workstation. Several cues are assigned to the point cloud to increase depth perception. Finally, a short theorem is proven that extends the domain of the inverse iteration method to a rotational family of quadratic quaternion Julia sets. >
Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic

Summary Restorative cell-based and pharmacological therapies for experimental stroke substantially improve functional outcome. These therapies target several types of parenchymal cells (including neural stem cells, cerebral endothelial cells, astrocytes, oligodendrocytes, and neurons), leading to enhancement of endogenous neurogenesis, angiogenesis, axonal sprouting, and synaptogenesis in the ischaemic brain. Interaction between these restorative events probably underpins the improvement in functional outcome. This Review provides examples of cell-based and pharmacological restorative treatments for stroke that stimulate brain plasticity and functional recovery. The molecular pathways activated by these therapies, which induce remodelling of the injured brain via angiogenesis, neurogenesis, and axonal and dendritic plasticity, are discussed. The ease of treating intact brain tissue to stimulate functional benefit in restorative therapy compared with treating injured brain tissue in neuroprotective therapy might more readily help with translation of restorative therapy from the laboratory to the clinic.
Covering conditions and algorithms for the synthesis of speed-independent circuits

This paper presents theory and algorithms for the synthesis of standard C-implementations of speed-independent circuits. These implementations are block-level circuits which may consist of atomic gates to perform complex functions in order to ensure hazard freedom. First, we present Boolean covering conditions that guarantee that the standard C-implementations operate correctly. Then, we present two algorithms that produce optimal solutions to the covering problem. The first algorithm is always applicable, but does not complete on large circuits. The second algorithm, motivated by our observation that our covering problem can often be solved with a single cube, finds the optimal single-cube solution when such a solution exists. When applicable, the second algorithm is dramatically more efficient than the first, more general algorithm. We present results for benchmark specifications which indicate that our single-cube algorithm is applicable on most benchmark circuits and reduces run times by over an order of magnitude. The block-level circuits generated by our algorithms are a good starting point for tools that perform technology mapping to obtain gate-level speed-independent circuits.
Application of agglomerative hierarchical clustering to identify consumer tomato preferences: influence of physicochemical and sensory characteristics on consumer response

A multiple regression model was developed to predict the acceptability of the four tomato varieties studied (Aranka, Cherry, Beef and Pitenza). Agglomerative hierarchical clustering showed the presence of four consumer clusters. One cluster preferred small tomatoes (Aranka and Cherry) and another cluster the larger tomatoes (Beef and Pitenza). In the sensorial analysis Aranka was the preferred variety, scoring more highly in taste, odour, acidity, sweetness and hardness. In the physicochemical analysis Aranka also obtained the highest values for titratable acidity (TA) and sugars (SSC), confirming that these parameters are important in tomato flavour. Lower values for both sets of parameters were reflected by lower consumer acceptability, with Beef and Pitenza receiving the lowest score for these flavours attributes (except odour). A significant correlation between the sensorial and physicochemical parameters was also observed: odour was positively correlated with calibre, while taste, acidity, hardness and acceptability were negatively correlated with calibre, pH and SSC/TA and positively correlated with SSC and TA.  2005 Society of Chemical Industry
The role of phrasal phonology in speech perception: What perceptual epenthesis shows us

Abstract Recent research using the phenomenon of illusory vowels has raised our awareness of the extent to which speech perception is modulated by the listener's native-language phonological knowledge. However, most of the focus has been limited to word-level phonological knowledge. In this article, we suggest that the perceptual system recruits segmental phonological knowledge that makes crucial reference to prosodic domains far beyond the word-level. We report the results from three identification experiments on Korean and American English participants. In accordance with their native-language phonotactic constraints at the level of the Intonational Phrase, Korean listeners unlike American English listeners hear more illusory vowels in stimuli containing the sequence of voiced stops followed by nasal consonants (e.g. [eɡma]) than those containing voiceless stops followed by nasal consonants (e.g. [ekma]). The results are interpreted as support for the view that speech perception makes crucial reference to the concept of reverse inference.
Adenocarcinoma in situ of the uterine cervix: a metaanalysis of 1278 patients evaluating the predictive value of conization margin status

Objective We sought to determine the value of conization margin status in predicting residual and recurrent adenocarcinoma in situ (ACIS) of the cervix. Study Design In all, 33 studies (1278 patients) were identified. Metaanalysis with pooled Mantel-Haenszel odds ratio (OR) was used to compare the risk of residual and recurrent disease according to margin status. Results A repeated excisional procedure was performed in 607 patients; a positive conization margin was associated with a significant increase in the risk of residual disease (OR, 4.01; 95% confidence interval [CI], 2.62-6.33; P P Conclusion After conization for ACIS, patients with positive margins are significantly more likely to have residual or recurrent disease, whereas those with negative margins may be treated conservatively.
Hallucinogenic plants: their earliest botanical descriptions.

(1979). Hallucinogenic Plants: Their Earliest Botanical Descriptions. Journal of Psychedelic Drugs: Vol. 11, Innovative Approached to Drug Abuse Treatment, pp. 13-24.
Purified, Soluble Recombinant Mouse Hepatitis Virus Receptor, Bgp1b, and Bgp2 Murine Coronavirus Receptors Differ in Mouse Hepatitis Virus Binding and Neutralizing Activities

Mouse hepatitis virus receptor (MHVR) is a murine biliary glycoprotein (Bgp1a). Purified, soluble MHVR expressed from a recombinant vaccinia virus neutralized the infectivity of the A59 strain of mouse hepatitis virus (MHV-A59) in a concentration-dependent manner. Several anchored murine Bgps in addition to MHVR can also function as MHV-A59 receptors when expressed at high levels in nonmurine cells. To investigate the interactions of these alternative MHVR glycoproteins with MHV, we expressed and purified to apparent homogeneity the extracellular domains of several murine Bgps as soluble, six-histidine-tagged glycoproteins, using a baculovirus expression system. These include MHVR isoforms containing four or two extracellular domains and the corresponding Bgp1b glycoproteins from MHV-resistant SJL/J mice, as well as Bgp2 and truncation mutants of MHVR and Bgp1b comprised of the first two immunoglobulin-like domains. The soluble four-domain MHVR glycoprotein (sMHVR[1-4]) had fourfold more MHV-A59 neutralizing activity than the corresponding soluble Bgp1b (sBgp1b) glycoprotein and at least 1,000-fold more neutralizing activity than sBgp2. Although virus binds to the N-terminal domain (domain 1), soluble truncation mutants of MHVR and Bgp1b containing only domains 1 and 2 bound virus poorly and had 10- and 300-fold less MHV-A59 neutralizing activity than the corresponding four-domain glycoproteins. In contrast, the soluble MHVR glycoprotein containing domains 1 and 4 (sMHVR[1,4]) had as much neutralizing activity as the four-domain glycoprotein, sMHVR[1-4]. Thus, the virus neutralizing activity of MHVR domain 1 appears to be enhanced by domain 4. The sBgp1b[1-4] glycoprotein had 500-fold less neutralizing activity for MHV-JHM than for MHV-A59. Thus, MHV strains with differences in S-glycoprotein sequence, tissue tropism, and virulence can differ in the ability to utilize the various murine Bgps as receptors.
The effects of noise on Occam's inversion of resistivity tomography data

An Occam's inversion algorithm for crosshole resistivity data that uses a finite-element method forward solution is discussed. For the inverse algorithm, the earth is discretized into a series of parameter blocks, each containing one or more elements. The Occam's inversion finds the smoothest 2-D model for which the Chi-squared statistic equals an a priori value. Synthetic model data are used to show the effects of noise and noise estimates on the resulting 2-D resistivity images. Resolution of the images decreases with increasing noise. The reconstructions are underdetermined so that at low noise levels the images converge to an asymptotic image, not the true geoelectrical section. If the estimated standard deviation is too low, the algorithm cannot achieve an adequate data fit, the resulting image becomes rough, and irregular artifacts start to appear. When the estimated standard deviation is larger than the correct value, the resolution decreases substantially (the image is too smooth). The same effects are demonstrated for field data from a site near Livermore, California. However, when the correct noise values are known, the Occam's results are independent of the discretization used. A case history of monitoring at an enhanced oil recovery site is used to illustrate problems in comparing successive images over time from a site where the noise level changes. In this case, changes in image resolution can be misinterpreted as actual geoelectrical changes. One solution to this problem is to perform smoothest, but non-Occam's, inversion on later data sets using parameters found from the background data set.
Sources of elevated salinity in the Mississippi River Alluvial Aquifer, south-central Louisiana, USA

Abstract Salinization is a process impacting groundwater quality and availability across much of southern Louisiana, USA. However, a broad divergence of opinion exists regarding the causes of this elevated salinity: updip-migrating marine waters from the Gulf of Mexico, saline fluids migrating up fault planes, movement of water from salt domes, and/or remnant seawater from the last major marine transgression. The Mississippi River Alluvial Aquifer (MRAA) in south-central Louisiana is recharged by the Mississippi River, and there are discharge zones to the west and east. Recharge waters from the Mississippi River are fresh, but Cl− levels in the western portions of the aquifer are as high as 1000 mg/L. The aquifer is an important source of water for several municipalities and industries, but prior to this study the source(s) of the elevated salinity or whether the salinization can be remediated had not been determined. The low Br/Cl ratios in the groundwaters are consistent with a saline endmember produced by subsurface dissolution of salt domes, not a marine source. The H and O isotopic systematics of the aquifer waters indicate meteoric sources for the H2O, not marine waters or diagenetically-altered deep brines. The westward salinization of aquifer water represents a broad regional process, instead of contamination by point sources. Mapping of spatial variations in salinity has permitted the identification of specific salt domes whose subsurface dissolution is producing waters of elevated salinity in the aquifer. These include the Bayou Choctaw and St. Gabriel domes, and possibly the Bayou Blue dome. Salinization is a natural, on-going process, and the potential for remediation or control is slight, if not non-existent.
Infection of Human Fetal Cardiac Myocytes by a Human Immunodeficiency Virus-1–Derived Vector

Cardiomyopathy associated with HIV-1 infection is a well-recognized complication. However, it is unknown whether direct cardiomyocyte infection is involved in the pathogenesis of the cardiomyopathy. An HIV-1-based lentiviral vector and wild-type HIV-1 were used to infect human fetal cardiac myocytes in a primary culture. Quantitative polymerase chain reaction, viral p24 antigen determination, and immunofluorescence were used to detect the synthesis of HIV-1 DNA and proteins after the infection. High-efficiency infection occurred using the HIV-1-based lentiviral vector, although no infection occurred with the wild-type HIV-1 strain. Dual-labeling immunofluorescence for HIV-1 proteins and myosin confirmed that cardiomyocytes were infected. This in vitro analysis suggests that direct myocyte infection with wild-type HIV-1 may not be involved in the pathogenesis of HIV-1 cardiomyopathy. However, HIV-1-based vectors may prove useful for ex vivo cardiovascular gene therapy.
Glucocorticoids Enhance or Spare Innate Immunity: Effects in Airway Epithelium Are Mediated by CCAAT/Enhancer Binding Proteins

Although it is widely accepted that glucocorticoids (GC) are a mainstay of the treatment of diseases characterized by airway inflammation, little is known about the effects of GC on local innate immunity. In this article, we report that respiratory epithelial cells manifested a local “acute phase response” after stimulation with TLR activation and TNF-α and that GC spared or enhanced the epithelial expression of molecules that are involved in host defense, including complement, collectins, and other antimicrobial proteins. As expected, GC inhibited the expression of molecules responsible for inflammation such as cytokines (IFNβ and GM-CSF) and chemokines (RANTES and IL-8). Studies using Western blotting, EMSA, and functional analysis indicated that the selective effects of GC are mediated through activation of the transcription factor C/EBP. Knockdown of C/EBPβ by small interfering RNA blocked the enhancement by GC of host defense molecule expression but had no effect on inflammatory gene expression. These results suggest that GC spare or enhance local innate host defense responses in addition to exerting anti-inflammatory actions. It is possible that the known ability of GC to reduce the exacerbation of diseases in which infectious organisms serve as triggering factors (e.g., asthma, allergic bronchopulmonary aspergillosis, and chronic obstructive pulmonary disease) may result in part from enhanced innate immune responses in airway mucosa.
Postoperative fluid collections after colon resection: the utility of clinical assessment

BACKGROUND: Computed tomography (CT) scans often identify postoperative fluid collections of uncertain clinical relevance.
Human Cyclin K, a Novel RNA Polymerase II-Associated Cyclin Possessing Both Carboxy-Terminal Domain Kinase and Cdk-Activating Kinase Activity

The gene coding for human cyclin K was isolated as a CPR (cell-cycle progression restoration) gene by virtue of its ability to impart a Far− phenotype to the budding yeast Saccharomyces cerevisiae and to rescue the lethality of a deletion of the G1 cyclin genes CLN1, CLN2, and CLN3. The cyclin K gene encodes a 357-amino-acid protein most closely related to human cyclins C and H, which have been proposed to play a role in regulating basal transcription through their association with and activation of cyclin-dependent kinases (Cdks) that phosphorylate the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II (RNAP II). Murine and Drosophila melanogaster homologs of cyclin K have also been identified. Cyclin K mRNA is ubiquitously expressed in adult mouse and human tissues, but is most abundant in the developing germ cells of the adult testis and ovaries. Cyclin K is associated with potent CTD kinase and Cdk kinase (CAK) activity in vitro and coimmunoprecipitates with the large subunit of RNAP II. Thus, cyclin K represents a new member of the “transcription” cyclin family which may play a dual role in regulating Cdk and RNAP II activity.
A Positive Right to Protection for Children

Concepts that are useful in other areas of human rights break down in the context of children. Because children are dependent on adults for their development, they are an anomaly in the liberal legal order, which views negative rights as implying fully rational, autonomous individuals that can exercise free choice. This Article argues for a positive right to protection for children, rooted in dignity, by probing the problematic nature of the positive/negative rights duality and exploring alternate legal approaches to protecting children’s rights in both international and comparative law. The adoption of positive rights for children would help assure adequate protection, which the current American legal regime, as typified by the case DeShaney v. Winnebago County Department of Social Services, fails to do.
Polymer-based vehicles for therapeutic peptide delivery

During the last decades increasing attention has been paid to peptides as potential therapeutics. However, clinical applications of peptide drugs suffer from susceptibility to degradation, rather short circulation half-life, limited ability to cross physiological barriers and potential immunogenicity. These challenges can be addressed by using polymeric materials as peptide delivery systems, owing to their versatile structures and properties. A number of polymer-based vehicles have been developed to stabilize the peptides and to control their release rates. Unfortunately, no single polymer or formulation strategy has been considered ideal for all types of peptide drugs. In this review, currently used and potential polymer-based systems for the peptide delivery will be discussed.
The Perils of Jointly Held General Powers of Appointment

This article provides an overview of the estate tax consequences of jointly-held general powers of appointment. To avoid triggering estate tax inclusion, a general power should be held with either the creator of the power or a person having a 'substantial' and 'adverse' interest in the exercise of the power. The determination that an interest is substantially adverse to the powerholder’s requires careful reference to the regulations. Jointly-held general powers of appointment are so complicated that they rarely are the most efficient drafting choice.
Interactive Design Optimization of Structural Systems

Considerable research has been recently conducted in developing and evaluating methods for optimum design of structural systems. Methods of design sensitivity analysis for static and dynamic response, shape optimization, and nonlinear response have been developed. In order to realize the full potential of these new developments, a highly flexible, user-friendly and interactive software environment is needed. Database design and management techniques, expert system techniques, and interactive graphics techniques can play a major role in creating a software environment for practical applications. The paper presents the state of the art in several of the above mentioned areas. Role of designer interaction in design of structures for static and dynamic response is explored and its advantages are discussed. A few simple example problems are used in presenting and evaluating the techniques.
Spending Shocks and Interest Rates

Most macroeconomic models imply that increases in aggregate demand due to non-monetary forces cause real interest rates to rise, but empirical evidence from the US generally fails to support this prediction. We propose a novel explanation for how increases in aggregate demand (driven either by public or private shocks) can have a zero or negative effect on interest rates: when national income is demand-determined and cash is used to cover short-term needs, government or private spending shocks may generate an excess supply of loans. Our model has three key features: (1) demand-determined output, (2) portfolio heterogeneity (as we have both borrowers and lenders), and (3) asset market segmentation (different groups adjust using different asset classes). Data from the Treasury’s General Account and the Survey of Consumer Finances support our premise that spending shocks are often financed with money-like assets. Evidence from the Consumer Expenditure Survey corroborates a key implication of our theory: demand shocks of rich savers decrease interest rates.
Enzymology of Protein Methylation: Recent Development

The presence of e-N-methyllysine was first observed in Salmonella typhimurium in 1959. Since this discovery the ubiquitous occurrence of protein methylation in nature has been well established (Paik & Kim, 1980). It involves N-methylation of lysine, arginine, histidine, alanine, proline, and glutamine, O-methylation of glutamic and aspartic acid, and S-methylation of methionine and cysteine (Paik & Kim, 1985). As shown in Table I, methylated amino acids occur in highly specialized proteins such as histones, flagella protein, myosin, actin, ribosomal proteins, opsin, EFlα(Tu), HnRNP protein, HMG-1 and HMG-2 protein, fungal and plant cytochrome c, myelin basic protein, porcine heart citrate synthase, heat-shock proteins, nucleolar protein, ferredoxin, wheat α-amylase, and calmodulin.
Loch, Stock and Two Spying Tales

Reasonable expectation of privacy has become the touchstone for determining invasion of privacy and search and seizure claims in common law countries. In the covert surveillance case of Kinloch v HM Advocate [2012] UKSC 62, [2013] 2 AC 93, Lord Hope invoked reasoning premised on the diminished privacy individuals can expect in public places. But by focusing solely on the actions of the individual, this enquiry fails to query the measures taken by the state itself. It can be contrasted to the case of Paton v Poole Borough Council IPT/09/01/C, 29 July 2010, where the Investigatory Powers Tribunal readily found that the Council’s own conduct in spying on the Paton family clearly interfered with their right to respect for their private and family life in a manner that was unnecessary, unlawful, and unreasonable.
Exploring Coral Reefs Using the Tools of Molecular Genetics

The tools of molecular genetics have been transformed over the last decades and have in turn transformed our understanding of coral reefs. Initially limited to information on single genes, we are now capable of analyzing entire genomes. These developments make it possible to do many things that were either impossible or extremely difficult before: identify cryptic species, microbes, larvae and gut contents; determine relationships among populations and species; characterize reproductive and dispersal patterns; infer mechanisms of speciation; and soon perhaps embark on genetic engineering. Notably, many aspects of coral reef conservation can and will increasingly benefit from insights derived from the application of molecular genetic tools.
Lessons Learned: One Universitys Experience In Developing And Revising An AIS Curriculum

The last decade has seen phenomenal growth in the use of technology and information systems in the field of accounting. In response to this change, many colleges and universities have added a concentration in Accounting Information Systems (AIS) to their accounting programs. This paper describes the processes followed by one comprehensive university to introduce and later revise an AIS concentration program. A surprising finding of the revision process was an unexpected role of the AIS courses in the alumnis career development, -- a finding which was uncovered only by an innovative investigative step of the review and revision process. In light of the results, a model is offered to assist other institutions in improving their curriculum development (and review) process.
Who Is a Pole and Where Is Poland? Territory and Nation in the Rhetoric of Polish National Democracy before 1905

At the turn of the twentieth century most Polish political activists dreamed of recreating the Polish state, although they disagreed about where the new Poland should be located and whom it should include. In the years before 1905 the National Democratic movement—the “Endecja,” as it was commonly called—envisioned an expansive Poland stretching from the Baltic to the Black Sea, and from the Dnieper to the Oder. How could a movement which came to be known for its pragmatism and tactical flexibility espouse such an unrealistic, if not absurd, ambition? How could nationalists who insisted upon cultural unity desire a nation which would include millions who neither spoke the Polish language nor considered themselves to be Poles? This article will argue that these questions can be illuminated by examining the Endecja's definition of that enigmatic Polish term, narod (nation).
Investigation on Organochlorine Pesticide Residues in Tea Samples Sailed in Zhuhai City

Objective To understand the situation of organochlorine pesticide residues in tea sailed in Zhuhai city.Method In 2006,the contents of HCH and DDT of 132 tea samples randomly collected from markets were determined by capillary gas chromatography according to national standard GB/T 5009.19—2003 "Determination of HCH and DDT residues in foods ".Results The detection rate of HCH was 40.9% and concentration was below the standard limit in all samples.The detection rate of DDT was 58.3%,and the over standard rate was 19.7%.Oolong tea exceeded the standard with the rate at 27.1%.Conclusion The Oolong tea sailed in Zhuhai city could be seriously contaminated by organochlorine pesticides.
Future antiepileptic drug development.

Article abstract-The last decade has seen an explosion in the number of antiepileptic drugs approved. Despite these advances, however, there are still other basic mechanisms of epilepsy that could be the targets of new agents. This article discusses some of these novel sites for possible antiepileptic drug action in the context of the available data supporting the various mechanisms. While not all of these investigations will be translated into clinically useful agents, there is still great unrealized potential for the development of new and novel antiepileptic compounds.
Congruent pattern of accessibility identifies minimal pore gate in a non-symmetric voltage-gated sodium channel

Opening and closing of the central ion-conducting pore in voltage-dependent ion channels is gated by changes in membrane potential. Although a gate residue in the eukaryotic voltage-gated sodium channel has been identified, the minimal molecular determinants of this gate region remain unknown. Here, by measuring the closed- and open-state reactivity of MTSET to substituted cysteines in all the pore-lining helices, we show that the state-dependent accessibility is delineated by four hydrophobic residues at homologous positions in each domain. Introduced cysteines above these sites do not react with intracellular MTSET while the channels are closed and yet are rapidly modified while the channels are open. These findings, in conjunction with state-dependent metal cross-bridging, support the notion that the gate residues in each of the four S6 segments of the eukaryotic sodium channel form an occlusion for ions in the closed state and are splayed open on activation. Gating of the central pore in voltage-dependent ion channels is mediated by changes in membrane potential. Here, the authors use substituted cysteine accessibility and metal cross-bridging to identify gate residues that form a physical occlusion when closed in a eukaryotic voltage-gated sodium channel.
Effects of novel acetylenic and allenic steroids on the rat prostate

Novel acetylenic and allenic steroid analogs previously have been synthesized in this laboratory and were shown to be potent irreversible inhibitors of delta5-3-ketosteroid isomerase from P. Testosteroni. This bacterial enzyme catalyzes the conversion of delta5-3-ketosteroids to the corresponding delta4-3-ketosteroids. These isomerizations are key steps in the mammalian biosynthesis of steroid hormones, and it was hoped that the acetylenic and allenic steroid analogs migh inhibit androgen biosynthesis. We have now shown that these compounds cause a significant and dose-dependent decrease in the wet weight of both ventral and dorsal lateral prostate in the mature male rat.
Global Land Surface Emissivity Estimation From AMSR2 Observations

A reliable estimate of emissivity is critical for a wide range of applications for the atmosphere, the biosphere, the lithosphere, the cryosphere, and the hydrosphere. This study uses three years (August 2012 to July 2015) of data from the Advanced Microwave Scanning Radiometer-2 sensor that is onboard the Global Change Observation Mission 1st Water satellite to explore estimates of instantaneous global land emissivity. A method is adopted to remove the known inconsistency in penetration depths between microwave brightness temperatures and infrared-based ancillary data that could cause differences between day and night emissivity estimates. After removing the diurnal atmospheric effects, the resulting retrieved cloud-free land emissivities realistically represent well-known large-scale features. As expected, the polarization differences of estimated emissivities show noticeable seasonal variations over the deciduous woodland and grassland regions due to changes in vegetation density. The potential of estimated emissivities for high-latitude snow detection and freeze/thaw state identification is also demonstrated.
Democracy and Coercive Diplomacy: Selective threats, effective threats: the initiation and escalation of international crises

The empirical analysis in this chapter centers around two effects which the informational perspective emphasizes: what I have referred to as the restraining and confirmatory effects. The restraining effect stems from the fact that governments that lack the ability to monopolize private information are less able to exploit information asymmetries through deception and bluff. Transparency and public competition mean that democratic governments face substantial constraints on their ability to make threats which they cannot or do not intend to carry out. The result, as we will see, is that governments so constrained are less likely to make militarized challenges against other states than are governments that have more leeway to engage in deceptive behavior. The confirmatory effect goes hand in hand with this restraining effect. In the narrow sense in which we used this term in Chapter 4, the confirmatory effect stems from the existence of a second information source – the opposition party – whose interests conflict with those of the government. This second signaler can credibly confirm the genuineness of the government's threat and thereby increase the likelihood that the rival state will back down. At a more general level, the confirmatory effect stems from the fact that, if a government is constrained from bluffing, then the threats which it does choose to make are more likely to be genuine than are the threats made by a government not similarly constrained. As a result, the target of a challenge from a democratic state should be less likely to resist than should the target of a threat made by a nondemocratic state.
The Effects of Trade between the US and Developing Countries on US Employment

The major objective of this paper is to attempt to estimate the effects of trade between the US and the developing world on US employment over the recent past. The paper is divided into four sections.
Against Levinas’ messianic politics: a polemic

Blamelessly, most commentators attempt to deduce the political theory of Levinas from his interhuman philosophy. In contrast to the perceived state of ethical life in contemporary politics, the attractiveness of the asymmetric obligations owed by the ego to the Other make the deductive project seem urgent. But an inductive analysis of Levinas’ philosophy yields troubling prerequisites, including rigorous theocracy and a form of sociability in which no epistemological clarity is permitted that could determine in situ interpersonal duties. Such unfamiliar politics enable the celebrated ethical relation of self for the Other. Designed as a polemic with the presumption that politics not ethics is first philosophy, the insights of the inductive analysis of Levinas’ thought will come as no surprise to observers who worry that power and sovereignty cannot be summarily excluded from social or even ethical relations.
Hitler, Mein Kampf: Eine kritische Edition

The Institut fur Zeitgeschichte (‘Institute of Contemporary History’) in Munich (IfZ) has published one of the most significant additions to scholarship about Adolf Hitler in the past 50 years. An ...
Examining Impulse-Variability Theory and the Speed-Accuracy Trade-Off in Children's Overarm Throwing Performance.

This study examined variability in throwing speed and spatial error to test the prediction of an inverted-U function (i.e., impulse-variability [IV] theory) and the speed-accuracy trade-off. Forty-five 9- to 11-year-old children were instructed to throw at a specified percentage of maximum speed (45%, 65%, 85%, and 100%) and hit the wall target. Results indicated no statistically significant differences in variable error across the target conditions (p = .72), failing to support the inverted-U hypothesis. Spatial accuracy results indicated no statistically significant differences with mean radial error (p = .18), centroid radial error (p = .13), and bivariate variable error (p = .08) also failing to support the speed-accuracy trade-off in overarm throwing. As neither throwing performance variability nor accuracy changed across percentages of maximum speed in this sample of children as well as in a previous adult sample, current policy and practices of practitioners may need to be reevaluated.
Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease.

Objective: To compare motor and nonmotor outcomes at 6 months of asleep deep brain stimulation (DBS) for Parkinson disease (PD) using intraoperative imaging guidance to confirm electrode placement vs awake DBS using microelectrode recording to confirm electrode placement. Methods: DBS candidates with PD referred to Oregon Health & Science University underwent asleep DBS with imaging guidance. Six-month outcomes were compared to those of patients who previously underwent awake DBS by the same surgeon and center. Assessments included an “off”-levodopa Unified Parkinson’s Disease Rating Scale (UPDRS) II and III, the 39-item Parkinson9s Disease Questionnaire, motor diaries, and speech fluency. Results: Thirty participants underwent asleep DBS and 39 underwent awake DBS. No difference was observed in improvement of UPDRS III (+14.8 ± 8.9 vs +17.6 ± 12.3 points, p = 0.19) or UPDRS II (+9.3 ± 2.7 vs +7.4 ± 5.8 points, p = 0.16). Improvement in “on” time without dyskinesia was superior in asleep DBS (+6.4 ± 3.0 h/d vs +1.7 ± 1.2 h/d, p = 0.002). Quality of life scores improved in both groups (+18.8 ± 9.4 in awake, +8.9 ± 11.5 in asleep). Improvement in summary index (p = 0.004) and subscores for cognition (p = 0.011) and communication (p Conclusions: Asleep DBS for PD improved motor outcomes over 6 months on par with or better than awake DBS, was superior with regard to speech fluency and quality of life, and should be an option considered for all patients who are candidates for this treatment. Clinicaltrials.gov identifier: NCT01703598. Classification of evidence: This study provides Class III evidence that for patients with PD undergoing DBS, asleep intraoperative CT imaging–guided implantation is not significantly different from awake microelectrode recording–guided implantation in improving motor outcomes at 6 months.
There goes the neighborhood: White-crowned Sparrow nest site selection and reproductive success as local density declines

ABSTRACT Changes in climate, vegetation, and land use are recognized as important drivers of changes in the distribution and abundance of wildlife. However, the behavioral and demographic mechanisms through which these changes affect populations have received less attention. Identifying these mechanisms is an important component of predicting the impacts of increasing environmental change. We used 30 yr of nest monitoring data at a study site where White-crowned Sparrow (Zonotrichia leucophrys) breeding density declined 85% to evaluate factors influencing habitat selection and reproductive success. Rapid secondary plant succession occurred at our study site, but the rate of change was faster in some areas than others. White-crowned Sparrows exhibited strong patterns of nest site selection, preferring open shrub vegetation and avoiding forest. As a result, many parts of the study area that were used for nesting early in the study period were no longer occupied by the end of the study period. Over the cours...
Development and implementation of a centralized comprehensive refill authorization program in an academic health system.

Purpose The development and implementation of a centralized, comprehensive, refill authorization (CCRA) program within an academic health system are described. Summary In order to improve continuity of care for our medically complicated patients, ambulatory pharmacy services developed and implemented a highly coordinated CCRA program for multiple community clinics within the system. To implement the CCRA program, we centralized the refill-request intake process to the Pharmacy Ambulatory Clinical Care Center (PAC 3 ). PAC 3 technicians were incorporated into the refill authorization process, and the collaborative practice agreement was updated to standardize the pharmacist refill approval process at the PAC 3 . We successfully standardized and centralized the medication refill process from 10 community clinics with 95 family practice and internal medicine providers and 26 medical residents. We handled an average of 12,000 refill requests each month, and pharmacists documented any interventions performed with each refill request. The cost savings associated with the CCRA program were attributed to the increased efficiency of the staff reviewing refill requests. The CCRA program increased the refill approval up to 10% compared with the previous decentralized refill authorization model. With the increased approval rate, the CCRA program saved 510 hours of our providers’ time annually, which created time for an additional 1,530 clinic visits. We demonstrated a faster average turnaround time for refill authorization, from an average of 72 hours before implementation to about 1 business day. Conclusion Implementation of an integrated refill authorization service standardized the method by which patients’ refill requests were addressed, increased refill efficiency, and improved refill authorization turnaround time.
High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth.

Abstract The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60–70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Our screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by our screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83%) have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18) of the inhibitory compounds have reported activity against dopamine receptors. We also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8 ± 12.8 ng/ml after 500 mg dose, inhibits S. neurona parasites at low concentrations (0.065 μM [0.036–0.12; 95% CI] or 21.9 ng/ml [12.1–40.3; 95% CI]). These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection.
Duty Cycle and Frequency Modulations in Class-E DC–DC Converters for a Wide Range of Input and Output Voltages

We present an operation scheme for a dc–dc converter consisting of a class-E inverter and a class-E rectifier to always achieve zero-voltage zero- $dv\text{/}dt$ switching at a wide range of input and output voltages. To cope with the high sensitivity due to load variations, previous approaches either forgo the zero- $dv\text{/}dt$ turn- on switching conditions or required additional components and topological changes. Instead, the proposed strategy modulates the duty cycles and switching frequencies depending on the input and output voltages to always achieve zero- $dv\text{/}dt$ turn- on switching and, thus, minimizes switching losses, while preserving the structural simplicity of the converter. Experiments demonstrate the prototype converter maintaining the desired soft-switching condition under 80–200-V input voltage and 5–20-V output voltage variations. In an additional prototype, we implemented a similar design with synchronous rectification that achieves a peak efficiency of 92.3% at an input voltage of 80 V, an output voltage of 12 V, and an output power of 26.9 W.
The carry-over effects of school gardens on fruit and vegetable availability at home: A randomized controlled trial with low-income elementary schools.

Abstract This group-randomized controlled trial examines the effects of a school garden intervention on availability of fruits and vegetables (FV) in elementary school children's homes. Within each region, low income U.S. schools in Arkansas, Iowa, New York, and Washington State were randomly assigned to intervention group (n = 24) or waitlist control group (n = 22). Children were in grades 2, 4, and 5 at baseline (n = 2768). The garden intervention consisted of both raised-bed garden kits and a series of grade-appropriate lessons. FV availability at home was measured with a modified version of the GEMS FJV Availability Questionnaire. The instrument was administered at baseline (Fall 2011) and throughout the intervention (Spring 2012, Fall 2012, Spring 2013). Analyses were completed using general linear mixed models. The garden intervention led to an overall increase in availability of low-fat vegetables at home. Among younger children (2nd grade at baseline), the garden intervention led to greater home availability of vegetables, especially, low-fat vegetables. Moreover, for the younger group, garden intervention fidelity (GIF) or robustness predicted home availability of fruit, vegetables, and low-fat vegetables. School gardens have potential to affect FV availability in the home environment.