cssi/SciSciGPT-SciSciNet huggingface dataset:
Patterns of treatment with everolimus exemestane in hormone receptor-positive HER2-negative metastatic breast cancer in the era of targeted therapy.

There is currently no clinical trial data regarding the efficacy of everolimus exemestane (EE) following prior treatment with CDK4/6 inhibitors (CDK4/6i). This study assesses the use and efficacy of everolimus exemestane in patients with metastatic HR+ HER2− breast cancer previously treated with endocrine therapy (ET) or endocrine therapy + CDK4/6i. Retrospective analysis of electronic health record-derived data for HR+ HER2− metastatic breast cancer from 2012 to 2018. The proportion of patients receiving EE first-line, second-line, or third-line, and the median duration of EE prior to next line of treatment (TTNT) by line of therapy was calculated. OS for patients receiving EE first-line, second-line, or third-line, indexed to the date of first-line therapy initiation and stratified by prior treatment received, was calculated with Kaplan-Meier method with multivariable Cox proportional hazards regression analysis. Six hundred twenty-two patients received EE first-line (n = 104, 16.7%), second-line (n = 273, 43.9%) or third-line (n = 245, 39.4%). Median TTNT was 8.3 months, 5.5 months, and 4.8 months respectively. Median TTNT of EE second-line was longer following prior ET alone compared to prior ET + CDK4/6i (6.2 months (95% CI 5.2, 7.3) vs 4.3 months (95% CI 3.2, 5.7) respectively, p = 0.03). Similarly, EE third-line following ET alone vs ET + CDK4/6i in first- or second-line resulted in median TTNT 5.6 months (95% CI 4.4, 6.9) vs 4.1 months (95% CI 3.6, 6.1) respectively, although this was not statistically significant (p = 0.08). Median OS was longer for patients who received EE following prior ET + CDK4/6i. EE second-line following ET + CDK 4/6i vs ET alone resulted in median OS 37.7 months vs. 32.7 months (p = 0.449). EE third-line following ET + CDK4/6i vs prior ET alone resulted in median OS 59.2 months vs. 40.8 months (p < 0.010). This difference in OS was not statistically significant when indexed to the start of EE therapy. This study suggests that EE remains an effective treatment option after prior ET or ET + CDK4/6i use. Median TTNT of EE was longer for patients who received prior ET, whereas median OS was longer for patients who received prior ET + CDK4/6i. However, this improvement in OS was not statistically significant when indexed to the start of EE therapy suggesting that OS benefit is primarily driven by prior CDK4/6i use. EE remains an effective treatment option regardless of prior treatment option.
Evaluation of guanidine-based multimodal anion exchangers for protein selectivity and orthogonality.

Abstract In this paper, we examined the chromatographic behavior of a new class of guanidine-based multimodal anion exchange resins. The selectivities and protein recoveries on these resins were first evaluated using linear gradient chromatography with a model acidic protein library at pH 5, 6 and 7. While a single-guanidine based resin exhibited significant recovery issues at high ligand density, a bis-guanidine based resin showed high recoveries of all but two of the proteins evaluated in the study. In addition, the bis-guanidine resin showed a more pH dependent selectivity pattern as compared to the low density single-guanidine resin. The salt elution range for the low density single-guanidine and bis-guanidine resins was also observed to vary from 0.250 to 0.621 M and 0.162 to 0.828 M NaCl, respectively. A QSAR model was then developed to predict the elution behavior of these proteins on the guanidine prototypes at multiple pH with overall training and test scores of 0.88 and 0.85, respectively. In addition, molecular dynamics simulations were performed with these ligands immobilized on a self-assembled monolayer (SAM) to characterize their conformational preferences and to gain insight into the molecular basis of their chromatographic behavior. Finally, a recently developed framework was employed to evaluate the separability of the bis-guanidine resin as well as its orthogonality to the multimodal cation exchanger, Nuvia cPrime. This evaluation was carried out using a second model protein library which included both acidic and basic proteins. The results of this analysis indicated that the bis-guanidine prototype exhibited both higher pair separability (0.73) and pair enhancement (0.42) as compared to the less hydrophobic commercial Nuvia aPrime 4A with pair separability and enhancement factors of 0.57 and 0.22, respectively. The enhanced selectivity and orthogonality of this new multimodal anion exchange ligand may offer potential opportunities for bioprocessing applications.
Soft powering the China Water Machine: the Bui Dam and China–Ghana relations

Although Ghana’s Bui Dam had been planned since 1915, it was only completed in 2013, with China’s financial and technical support. The Ghanaian government touted this breakthrough as crucial in add...
Automated detection and segmentation of sclerotic spinal lesions on body CTs using a deep convolutional neural network.

To develop a deep convolutional neural network capable of detecting spinal sclerotic metastases on body CTs. Our study was IRB-approved and HIPAA-compliant. Cases of confirmed sclerotic bone metastases in chest, abdomen, and pelvis CTs were identified. Images were manually segmented for 3 classes: background, normal bone, and sclerotic lesion(s). If multiple lesions were present on a slice, all lesions were segmented. A total of 600 images were obtained, with a 90/10 training/testing split. Images were stored as 128 × 128 pixel grayscale and the training dataset underwent a processing pipeline of histogram equalization and data augmentation. We trained our model from scratch on Keras/TensorFlow using an 80/20 training/validation split and a U-Net architecture (64 batch size, 100 epochs, dropout 0.25, initial learning rate 0.0001, sigmoid activation). We also tested our model’s true negative and false positive rate with 1104 non-pathologic images. Global sensitivity measured model detection of any lesion on a single image, local sensitivity and positive predictive value (PPV) measured model detection of each lesion on a given image, and local specificity measured the false positive rate in non-pathologic bone. Dice scores were 0.83 for lesion, 0.96 for non-pathologic bone, and 0.99 for background. Global sensitivity was 95% (57/60), local sensitivity was 92% (89/97), local PPV was 97% (89/92), and local specificity was 87% (958/1104). A deep convolutional neural network has the potential to assist in detecting sclerotic spinal metastases.
The Art of Breeding Art

Strangely enough, the insight that inspired this book originated in a then unique (and exotic) experiment in online picture breeding. This chapter tells the story of that experiment and how it led to the unexpected insight that objectives can thwart discovery. Because it appeared it might lead to something interesting, we created a online system where users on the internet could collaborate to discover pictures. It turned out that many users enjoyed the system and together they found many interesting and complex pieces of art. However, the surprising outcome was that the most impressive and popular pictures on the site were the product of users who weren’t focused on discovering anything in particular. In other words, abandoning objectives led to the best outcomes. Considering this strange result led us to question whether this phenomenon was true not only in breeding pictures, but if it also holds for broader systems of innovation and discovery.
Weak instrument inference in the presence of parameter instability

Summary This paper addresses the question of how to conduct inference on weakly identified coefficients in unstable econometric models. The weak correlations between the instruments and the relevant first-order condition are modelled as local to zero, and we focus on moderate parameter instabilities. We show that, in the presence of weak identification, asymptotic distributions on the estimators and tests remain robust to moderate instability. Therefore, inference on the subset of stable parameters remains robust to moderate instability of nuisance parameters. In addition, in an unstable model where some parameters are weakly identified, weak-instrument asymptotics in the literature can be used to make valid inference for the weakly identified coefficients after the strongly identified coefficients are concentrated out.
William James on Ethics and Faith

Introduction: a practical faith Part I. Practical Faith and the Will to Believe: 1. The will and the right to believe 2. James's Wager and the right to believe Part II. Two Moral Arguments for Religious Faith: 3. James's religious ethics in 'The Moral Philosopher and the Moral Life' 4. Overcoming pessimism in 'Is Life Worth Living'? Part III. Piecemeal Supernaturalism and Practical Needs: 5. Religion and morality in the varieties of religious experience 6. A pragmatic account of religion Epilogue Bibliography Index.
The role of polysaccharide in the secretion of protein by Micrococcus sodonensis.

Abstract Cell suspensions of Micrococcus sodonensis (ATCC 11880) secrete 7 to 10 individual proteins including an alkaline phosphatase, a nuclease, and a protease. The appearance of enzyme activities in the extracellular medium is dependent on the co-secretion of at least one of several polysaccharides also elaborated by these cells. This conclusion is based on the following observations: (a) bacitracin, an inhibitor of polysaccharide biosynthesis, proportionately inhibits polysaccharide and protein secretion at concentrations which have no effect on intracellular protein synthesis; (b) a mutant, impaired in its ability to secrete proteins, is also impaired in its ability to secrete a glucosamine-rich polysaccharide; (c) alkaline phosphatase secretion by mutant protoplasts is enhanced in the presence of exogenously supplied polysaccharide; (d) inclusion of 10 mm glucosamine or 2-deoxyglucose (a variety of other monosaccharides were ineffective) in the medium suppresses the secretion of all three enzymes as well as the glucosamine-containing polysaccharide; and (e) restoration of alkaline phosphatase secretion in glucosamine-inhibited protoplasts is achieved by the addition of purified preparations of the glucosamine-containing polysaccharide. The inhibition of enzyme secretion by either glucosamine or 2-deoxyglucose can be completely prevented or reversed by addition of equimolar concentrations of glucose. The addition of albumin or casein to glucosamine-inhibited cells markedly enhances the rate of alkaline phosphatase secretion. These results suggest that during secretion polypeptide chains are vulnerable to proteolytic degradation and that co-secretion of polysaccharide protects the protein from proteolysis.
The microflora of grassland.

Publisher Summary The role of microscopically small organisms in numerous soil processes, particularly those affecting plant productivity, is well recognized. Less well known is the quantity of recently gathered information concerning microorganisms as the components of major plant communities and the extent to which they participate in the total energy flow therein. Although the soil microflora is the single most important group in the annual turnover of energy trapped by photosynthesis, no broad general review of the microflora of grassland has heretofore been compiled. There is a rich microflora associated with the surfaces of living plants that is either nonpathogenic or at most functioning at an extremely marginal level of pathogenicity. This microflora feeds primarily on exudates and sloughed cellular material. It commonly is divided into two categories: (a) the aboveground, shoot-associated microflora, or broadly referred as the “phyllosphere” and (b) the belowground, root-associated microflora, broadly referred as the “rhizophere.” This chapter examines the microflora of grassland litter, the microflora of grassland soils, biomass and bioactivity measurements, the humic component of grassland soil, and nitrogen transformations in grassland soils.
Treatment of an Unusual Adolescent Bed-Wetting Behavior by Covert Sensitization

Abstract. A bizarre bed-wetting behavior in an adolescent male was treated successfully by the technique of covert sensitization. The target behavior disappeared completely after the third week of treatment, and had not recurred two years later. In addition, other positive changes in the patient's behavior were noted. The discussion is centered on the appropriateness of short-term symptom-reducing intervention with adolescents, facilitation of "ripple effect," and the advantages of minimal labeling of psychopathology
January Effect - A Re-examination

The multitude of explanations for the January effect leaves the reader confused about its primary cause(s): is it tax-loss selling, window-dressing, information, bid-ask bounce, or a combination of these causes? The confusion arises, in part, because evidence has been presented in support of a particular hypothesis though the same evidence may be consistent with more than one hypothesis. Furthermore, prior work has not adequately controlled for the bid-ask bounce. In this paper, we try to disentangle different explanations of the January effect and identify its primary cause. We find that tax-related selling is the most important cause, overshadowing other possible explanations.
Some theoretical considerations of articulation substitution phenomena.

Articulation substitutes in the speech samples of American children, grades one through six, representing standard American English, Black English, and Spanish-influenced-English were analysed using a distinctive features approach. Results indicated that beyond variations due to dialect and second language influences, most substitutions could be predicted from phonemic complexity criteria developed from phonological theory. Specially, markedness theory was demonstrated as a basis of predicting the phonetic feature characteristics of substitutions.
Amino Acid Diets and Maximal Growth in the Rat

Amino acid diets fed in an agar gel have been found to support weight gains of rats as great or greater than those obtained with diets containing an equiva lent quantity of casein supplemented with methionine. Over 1% arginine, 0.6% asparagine and feeding the diet in gel form were necessary to obtain maximal weight gain. The diet contained amino acids in excess of the requirements of the rat, and hence it should be possible to improve the efficiency of utilization of the amino acid mixture. It was not until after the extensive in vestigations of Rose and co-workers had culminated in the discovery of threonine that amino acid diets of known composi tion could be prepared which would sup port growth. At the close of their work, Rose and associates (1) had developed amino acid diets that would support a moderate rate of growth but not a rate equivalent to that obtained with diets con taining intact protein. When it was ob served that intact protein increased weight gain of animals fed amino acid diets, the growth-stimulating factor was for some time considered to be peptide in nature. For example, Woolley (2) observed that a supplement of 2% of casein improved the growth of mice fed an amino acid diet and attributed the increased growth rate to a peptide growth factor which he isolated from enzymatic digests and designated strepogenin. A few years later Maddy and Elvehjem (3) reported equivalent growth rates for mice fed whole casein or an amino acid diet. Still later, however, (1952) Maddy and Swift (4) were not able to achieve maximal weight gains in rats fed amino acid diets. The quantity of protein required in amino acid diets for maximal growth of the rat is in fact, large. In table 1 are listed the weight gains of rats fed a complete amino acid diet, supplemented with in creasing increments of casein. Twelve per cent of casein was required before weight gain was equivalent to that of rats fed a diet containing 20% casein. (The amino acids in the diet did not prevent maximal weight gain from being attained.) From the late 1940's until the present there has been considerable controversy over the question of whether there is a specific compound in protein which in creases the growth rate of animals fed an amino acid diet. There have been several reports that amino acid diets supported growth rates equivalent to these obtained with diets containing intact protein and an even greater number indicating that protein would stimulate the growth of rats fed amino acid diets. An examination of the literature indicates that maximal growth rate has, in fact, never been ob tained routinely. One question has been the importance of using only the L-isomers of amino acids as compared with adding appreciable quantities of u-amino acids to the diets.
Firm's Forecasts of Engineering Employment

In this paper we present data concerning the accuracy of firm's forecasts of engineering employment and suggest a simple model that may be of use in improving their accuracy. The results, which pertain to 54 firms in the aerospace, electronics, chemical, and oil industries, should be of use to managers, because the formulation of proper manpower policies clearly depends on the precision of such forecasts. Our approach also may be applicable to personnel other than engineers: better forecasts may result from the application of this simple model.
Shell game: A three-choice, contingent procedure for probability learning

Abstract Five groups composed of 24 college students each were run in a three-choice probability learning experiment in which information was given only concerning correct responses. Different groups received different assignments of reinforcement probabilities to the three choices. Major findings of this investigation were (i) asymptotic response probability approximated probability matching if reinforcement probabilities summed to unity, and (ii) for all reinforcement schedules, statistics of the data were well described by the linear or n-element models of statistical learning theory using the assumption that following incorrect responses, response probability was redistributed in a constant ratio of the probabilities of the reinforcements associated with the remaining alternatives.
The attribution of perceptual fluency in recognition memory: the role of expectation

Abstract Three experiments investigate whether the influence of perceptual fluency on recognition memory depends on a perceptual match between study and test. The perceptual fluency of recognition test items was enhanced by briefly presenting a prime that matched the subsequent test item. Enhanced perceptual fluency increased positive recognition responses when the study and test were in the same sensory modality but not when the study and test were in different modalities. This interaction occurred only when modality was manipulated between subjects; when modality was manipulated within subjects, enhanced perceptual fluency increased positive recognition responses to all test items. An interaction between modality and perceptual fluency was also found using “counterfeit” study lists. The results suggest that the use of perceptual fluency as a heuristic in recognition memory depends on whether it is perceived as relevant to the recognition decision.
A fast projector-backprojector pair modeling the asymmetric, spatially varying scatter response function for scatter compensation in SPECT imaging

Slab derived scatter estimation (SDSE) accurately models the asymmetric, spatially varying scatter response function in uniformly attenuating objects with convex surfaces. This model is implemented in a projector-backprojector that, when combined with iterative reconstruction techniques, provides accurate scatter compensation in single-photon emission computed tomography (SPECT). These iterative reconstruction-based scatter compensation techniques have the advantage that they use all detected photons, avoiding the noise amplification occurring with subtraction based schemes. Scatter compensation with iterative reconstruction does not involve the use of arbitrary adjustable parameters. A new fast algorithm for implementing SDSE that reduces computation time by a factor of 16 compared to a direct implementation is presented. Projection data computed with the new algorithm compare well with data from Monte Carlo simulations. >
Protective effect of practice on cognition during aging: implications for predictive characteristics of performance and efficacy of practice

In the present study, the effect of previous experience on spatial memory, which required the retention of information either over long intervals or within a single session, was longitudinally tested in the water maze in male F-344 rats that were from 6 to 24 months of age. Performance in these tasks was found to be age-dependent (Markowska, 1999). Other behavioral tasks in the straight alley and with a visible platform in the water maze controlled the noncognitive components of performance. For all tasks, performance was significantly correlated between 12-month-old and 18-month-old rats, indicating that cognitive performance at the early, but not advanced, stage of aging could be predicted from performance at a younger age if the novelty of the first exposure to the task was eliminated. The protective effect of experience was more robust in the reference memory task as compared to the working memory task and was modified by age when training was initiated. Behavior during the probe trials was more sensitive to the effect of aging and more resistant to the beneficial effect of practice as compared to the performance in the platform trials. The speed of swimming of experienced rats progressively decreased with age only when tested in the cognitive tasks but not in the straight alley. This indicates that speed of swimming during cognitive tasks does not exclusively reflect the ability to swim, but might be also affected by the cognitive demands of the task. Protective effect of experience on cognition was not modified by restriction in diet.
Biochemical characterization of enzyme fidelity of influenza A virus RNA polymerase complex.

Background It is widely accepted that the highly error prone replication process of influenza A virus (IAV), together with viral genome assortment, facilitates the efficient evolutionary capacity of IAV. Therefore, it has been logically assumed that the enzyme responsible for viral RNA replication process, influenza virus type A RNA polymerase (IAV Pol), is a highly error-prone polymerase which provides the genomic mutations necessary for viral evolution and host adaptation. Importantly, however, the actual enzyme fidelity of IAV RNA polymerase has never been characterized. Principal findings Here we established new biochemical assay conditions that enabled us to assess both polymerase activity with physiological NTP pools and enzyme fidelity of IAV Pol. We report that IAV Pol displays highly active RNA-dependent RNA polymerase activity at unbiased physiological NTP substrate concentrations. With this robust enzyme activity, for the first time, we were able to compare the enzyme fidelity of IAV Pol complex with that of bacterial phage T7 RNA polymerase and the reverse transcriptases (RT) of human immunodeficiency virus (HIV-1) and murine leukemia virus (MuLV), which are known to be low and high fidelity enzymes, respectively. We observed that IAV Pol displayed significantly higher fidelity than HIV-1 RT and T7 RNA polymerase and equivalent or higher fidelity than MuLV RT. In addition, the IAV Pol complex showed increased fidelity at lower temperatures. Moreover, upon replacement of Mg(++) with Mn(++), IAV Pol displayed increased polymerase activity, but with significantly reduced processivity, and misincorporation was slightly elevated in the presence of Mn(++). Finally, when the IAV nucleoprotein (NP) was included in the reactions, the IAV Pol complex exhibited enhanced polymerase activity with increased fidelity. Significance Our study indicates that IAV Pol is a high fidelity enzyme. We envision that the high fidelity nature of IAV Pol may be important to counter-balance the multiple rounds of IAV genome amplification per infection cycle, which provides IAV Pol with ample opportunities to generate and amplify genomic founder mutations, and thus achieve optimal viral mutagenesis for its evolution.
Present time perspective as a predictor of risky driving

This research introduces a new individual difference variable, time perspective, as an important predictor of risky driving. Across three separate replications, with 2863 participants, present time perspective is significantly correlated with reported risky driving behaviors. Its effect is greater than, and independent of, the negative correlations between future time perspective and risky driving. Additionally, males are more present-oriented and report taking more risks than females, while females are more future-oriented. Regression analyses and discriminate validity assessments demonstrate that present time perspective remains an independent predictor of risky driving even when pitted against nine other measures previously reported as related to driving risk, such as, sensation seeking, impulsivity, and aggression. Although complicated by the number of factors potentially involved, it is imperative to attempt to predict such risk because of the enormous economic and psychological toll resulting from auto accidents and fatalities related to risky driving. Discussion centers on implications for education based on understanding the psychological dynamics of time perspective and links to general risk-taking and self-regulation. Language: en
Functional Gene Variation in the Human Norepinephrine Transporter

The norepinephrine (NE) transporter (NET) is responsible for the re-uptake of NE into presynaptic nerve terminals, thus critically regulating noradrenergic signaling and homeostasis. Since NE signaling contributes to diverse brain functions, we hypothesize that promoter variation within the human NET gene (solute carrier family 6, member 2; SLC6A2) may impact risk for NE-related disorders, including depression, attention deficit hyperactive disorder (ADHD), and autonomic dysfunction. In support of this, we recently found a functional polymorphism at -3081 position upstream of the transcription initiation site. This polymorphism displayed differential promoter function, which we showed could arise from recruitment of a transcriptional repressor. Further analyses identified Slug and Scratch as candidates involved in repression of SLC6A2 transcription generated by the -3081(T) allele. Moreover, we observed a significant association of the -3081(T) variant with ADHD. Altered transcription of SLC6A2 may therefore represent a novel risk factor for the development of ADHD.
Development of two synthetic routes to CE-178,253, a CB1 antagonist for the treatment of obesity

Abstract CE-178,253 benzenesulfonate (1) is a CB1 antagonist discovered by Pfizer medicinal chemists. Two syntheses of this compound are described. The first, based on the discovery synthesis, involves assembly of an aryl-substituted pyrazolotriazine core onto which the second aryl moiety is installed by a Suzuki coupling; this route has been scaled to provide up to 6 kg of API. A second, more convergent route is also described, which installs the pyrazolotriazine containing both aryl substituents by condensation of a bromoketone with a substituted thiosemicarbazide. This route has been demonstrated on laboratory scale and is viewed as the preferred bond-forming sequence.
Structure characterization and strain relief analysis in CVD growth of boron phosphide on silicon carbide

Abstract Boron phosphide (BP) is a material of interest for development of a high-efficiency solid-state thermal neutron detector. For a thick film-based device, microstructure evolution is key to the engineering of material synthesis. Here, we report epitaxial BP films grown on silicon carbide with vicinal steps and provide a detailed analysis of the microstructure evolution and strain relief. The BP film is epitaxial in the near-interface region but deviates from epitaxial growth as the film develops. Defects such as coherent and incoherent twin boundaries, dislocation loops, stacking faults concentrate in the near-interface region and segment this region into small domains. The formation of defects in this region do not fully release the strain originated from the lattice mismatch. Large grains emerge above the near-interface region and grain boundaries become the main defects in the upper part of the BP film.
Methods of measuring citizen board accomplishment in mental health and retardation.

The presidents of all 37 Massachusetts Mental Health and Retardation (catchment) Area Boards were interviewed. Analysis of interview information yielded quantitative measures of citizen board accomplishment in community mental health: the Short Index of Accomplishment; the Global Assessments; and four orthogonal factors measuring accomplishment. The methods and instruments devised in this study should be valuable to researchers evaluating citizen boards. Moreover the four orthogonal factors found can be considered indicators of four conceptually different types or strategies of accomplishment: service creation, mobilization of outside resources, local autonomy, and coordination. These may apply to citizen boards of many kinds.
Investigation of Hydrological Variability in West Africa Using Land Surface Models

Abstract The availability of freshwater is a particularly important issue in Africa where large portions of the continent are arid or semiarid and climate is highly variable. Sustainable water resource management requires the assessment of hydrological variability in response to nature climate fluctuation. In this study, a land surface model, the Integrated Biosphere Simulator (IBIS), and a hydrological routing model, the Hydrological Routing Algorithm (HYDRA), are used to investigate the hydrological variability in two large basins, the Lake Chad basin (LCB) and the Niger River basin (NRB), located in West Africa, over the period from 1950 to 1995. The IBIS land surface hydrological module was calibrated and validated for arid and semiarid Africa, and major enhancements were made to the module, including the development of a dynamic root water–extraction formulation, the incorporation of a Green–Ampt infiltration parameterization, and modification to the prescribed root distribution, the runoff module, a...
W14-01 Reinventing the wheel in clinical trial design

Recent publications by the Institute of Medicine have unearthed several fundamental flaws in clinical trial methodology that, if corrected by the next generation of clinical investigators, can transform the field of mental health intervention research. Using a clinician-friendly approach, this workshop will succinctly review the essential elements of optimal design and implementation of a randomized controlled clinical study and the strategies to enhance signal detection. These include minimizing bias in the estimate of treatment effect while maintaining a nominal level of type I error (i.e., false positive results) and maintaining sufficient statistical power (i.e. reducing the likelihood of false negative results). Particular attention will be paid to reducing the problems of attrition and the hazards of multiplicity. Methods to examine moderators of the treatment effect will also be explored. Examples from psychopharmacologic, psychotherapy, and vocational rehabilitation trials for the treatment of posttraumatic stress disorder, depression, and panic disorder will be provided to illustrate these issues. Techniques to reduce the study's costs, risks, and participant burden will be described. Following the didactic session, the participants are encouraged to bring forth their own questions regarding clinical trial design for a 45-minute interactive discussion with the presenters. The objectives of the workshop are to improve the participants’ understanding of the goals of clinical trial design and methods to achieve those goals in order to improve their own research techniques, grantsmanship, and abilities to more accurately judge the results of studies presented in the literature.
DO IMPERFECT TRADE‐OFFS AFFECT THE EXTINCTION DEBT PHENOMENON?

A tight trade-off between competitive and colonization abilities is a key assumption of so-called “extinction debt models.” This trade-off implies that species ranked high in competitive ability will be ranked low with respect to dispersal. Although such a strict trade-off is plausible as a general trend, there are many examples in nature of deviations from perfect trade-offs. To determine how robust the “extinction debt” phenomenon is to imperfect trade-off relationships, I reexamined the extinction debt model of Tilman et al. in light of imperfect trade-offs. Numerically solving a system of differential equations, I found that, although the extinction debt phenomenon is not eliminated by the presence of imperfect trade-offs, the loss of species occurs earlier (with less habitat destruction) and more linearly than with perfect trade-offs.
Representationless Formalism in the Field Theory of Fixed Nucleons

The usual approach to field theory, in which state vectors are expanded in terms of eigenvectors of ${H}_{0}$, is known to be inconsistent for point particles. An alternative method, in which only quantities bilinear in physical state vectors are considered, avoids this inconsistency. For the simplest case, the fixed point nucleon interacting with scalar charge-symmetric mesons, meaningful equations without infinite renormalization constants are obtained, and expansion in terms of the renormalized coupling constant $f$ gives finite observables of one type. Observables "of the second kind," such as the interaction energy with an external field, cannot be defined as power series in $f$, but as limits of the quotients of two power series in $f$. The method is applied to the calculation of the magnetic nucleon moment in the static cutoff model with pseudovector coupling. Third and fifth approximations are calculated, and satisfactory convergence seems to prevail. The results are in agreement with experiments for the vector part of the moment, but the scalar part cannot be calculated on this model.
The bonding in N-trimethylsilylaniline

THE BONDING IN N-TRIMETHYLSILYLANILINE Claude H. Yoder Department of Chemistry Franklin and Marshall College Lancaster, Pennsylvania 17604 (Received II December 1970) The bonding in N-trimethylsilylaniline has been a subject of recent concern. Randall and Zuckerman's report of no stereochemical evidence for (p-d)~-overlap in the Si-N bond was based upon the lower 15N-H coupling constant in the 15N isotopomer relative to 15N-aniline (I). This argument has been criticized on several counts: a) (p-d)~-overlap can obtain between an s-p hybrid orbital (e.g. sp 3) on nitrogen and a d -orbital on silicon and thus T-overlap need not be accompanied by a serious change in hybridization and 15N-H coupling constant (3), and b) N-substitution of silicon for hydrogen in aniline might simply result in the diversion of some ~-bonding from the Car-N bond to the N-Si bond causing again little or no change in the electronic nature of the N-H bond (4). In an attempt to clarify the bonding in this system we have synthesized and obtained the 19F chemical shifts in the compounds F~NM(CH3)3'~H where M=C and Si. If o-(electronegativity)
Elementary cognitive tasks and their roles in g estimates

In this study, we examined the relationship between elementary cognitive tasks (ECTs) and the general factor, or g, of intelligence. We investigated the pattern of correlations of these tasks with estimates of g, and their roles in g estimates when g estimates were used to explain scholastic performance. We found that, in addition to a general information processing component, there is a memory processing component, nonchronometric in nature, that substantially contributes to g estimates. We also found that using ECTs to define g, along with traditional psychometric tasks, does not significantly alter the axis of g in relation to the axis of the scholastic performance factor in the factorial space. In other words, the predictive power of g will not be compromised when g is defined using experimentally more tractable ECTs. The theoretical and practical implications of such findings were discussed.
Crosstalk fault detection by dynamic Idd

Undesired capacitive crosstalk between signals is expected to be a significant concern in deep submicron circuits. New test techniques are needed for these crosstalk faults since they may cause unacceptable performance degradation. We analyze the impact of crosstalk faults on a circuit's power dissipation. Crosstalk faults can be detected by monitoring the dynamic supply current. The test method is based on a recently developed dynamic Idd test metric, the energy consumption ratio (ECR). ECR-based test has been shown to be effective at tolerating the impact of process variations. In this paper, we apply a ECR-based test method called ECR-VDD test to detect the crosstalk faults. The effectiveness of the method is demonstrated by simulation results.
The Genetic Basis for Bacterial Mercury Methylation

Methylmercury is a potent neurotoxin produced in natural environments from inorganic mercury by anaerobic bacteria. However, until now the genes and proteins involved have remained unidentified. Here, we report a two-gene cluster, hgcA and hgcB, required for mercury methylation by Desulfovibrio desulfuricans ND132 and Geobacter sulfurreducens PCA. In either bacterium, deletion of hgcA, hgcB, or both genes abolishes mercury methylation. The genes encode a putative corrinoid protein, HgcA, and a 2[4Fe-4S] ferredoxin, HgcB, consistent with roles as a methyl carrier and an electron donor required for corrinoid cofactor reduction, respectively. Among bacteria and archaea with sequenced genomes, gene orthologs are present in confirmed methylators but absent in nonmethylators, suggesting a common mercury methylation pathway in all methylating bacteria and archaea sequenced to date.
Sustained Release from Inert Wax Matrixes II: Effect of Surfactants on Tripelennamine Hydrochloride Release

Abstract The influence of several surfactants on the in vitro release of tripelennamine hydrochloride from a wax matrix was investigated. The congealed mass, obtained by dispersing the drug and surfactant in a molten mixture of carnauba wax and stearyl alcohol, was granulated and compressed into cores. While controlling particle-size distribution, tablet hardness, and weight, dissolution in simulated intestinal fluid was measured with the rotating-basket method. Water-insoluble surfactants such as glyceryl monostearate had no effect on the dissolution rate; slightly soluble or slowly soluhle agents, such as sodium stearate, ammonium stearate, triethanolarnine, and dioctyl sodium sulfosuccinate moderately increased dissolution. However, the water-soluhle hydrophilic polyoxyethylene 23 lauryl ether considerably increased the dissolution rate; i.e. , about 80% of drug was released by a zero-order process over 4 hr. Since only a few surfactants were investigated, it is difficult to explain the difference in dissolution rate on the basis of ionic character. The profound effect of polyoxyethylene 23 lauryl ether could be attributed to both its hydrophilic nature and wetting action in an aqueous environment at the liquid-solid interface. Only with polyoxyethylene 23 lauryl ether was more than 50% released over 8 hr. With no surfactant present, approximately 38% was released, and release in the 1st hr was most rapid. The data suggest that a surfactant may make more channels available for the dissolution fluid to leach out the drug. Thus, the effective porosity of the matrix is increased. Furthermore, wetting is an important factor that controls matrix permeability.
Comment on: On Improper Integrals in the Depolarization Dyadics of Lossless Gyrotropic Media, and the Maxwell Garnett Formalism by Dmitri A. Marakassov (in AEÜ, Vol. 55 (2001), 252–259)

Summary A “strange and unexpected result” presented recently by Marakassov [AEU 55 (2001), 252–259] is intrinsically incorrect.
Formal Requirements Analysis Techniques for Software-Intensive Automotive Electronic Control Systems

The ever increasing number and complexity of software-controlled features in today's automotive vehicles mandate the use of numerous techniques and tools for ensuring the absence of any kind of defects in them. In this connection, one of the key areas of applied research today involves the identification, development and use of various analyses on Feature Requirements so that any defects can be caught early in the system development lifecycle. In this paper, the following aspects will be covered: 1) an overview of various analyses available within current commercial requirements tools, 2) a discussion on what additional analyses at the requirements level would be desirable to help various stakeholders in the system development lifecycle, 3) an overview of what GM R&D has been developing/have developed to-date in order to identify or help identify various kinds of defects and thereby improve the requirements, 4) some key results and experiences in utilizing such analyses in one/more pilot applications and 5) a discussion of how the benefits of both current and new techniques and tools can be made use of in the development of new software -based automotive electronic control systems.
Intraocular injection of tetrodotoxin in goldfish decreases fast axonal transport of [3H]glucosamine-labeled materials in optic axons

When physiological activity in goldfish visual system was abolished by repeated intraocular injection of tetrodotoxin (TTX), the fast axonal transport of radioactive amino acid-labeled protein in the optic axons was unaltered. However, the TTX treatment reduced the amount of [3H]glucosamine-labeled glycolipids that were axonally transported to the optic tectum, and may have decreased their rate of turnover in the tectum. A similar though smaller effect was observed for glucosamine-containing glycoproteins. These alterations in axonal transport may be the basis for at least some of the deleterious effects of TTX on axonal regeneration in this system.
Electroweak and finite quark-mass effects on the Higgs boson transverse momentum distribution

We perform a detailed study of the various one-loop contributions leading to production of the standard model Higgs boson in association with a hard jet. This production mode contributes to the current Tevatron exclusion limit of the standard model Higgs with $160\text{ }\text{ }\mathrm{GeV}\ensuremath{\le}{M}_{H}\ensuremath{\le}170\text{ }\text{ }\mathrm{GeV}$, and will also be important for discovery and interpretation of new scalar bosons at the Large Hadron Collider (LHC). We include top- and bottom-quark initiated contributions, maintaining the exact dependence on the quark masses, and also study previously neglected $W$- and $Z$-boson mediated effects which shift the $qg$ and $q\overline{q}$ production modes. We consider the deviations from commonly used approximations for the Higgs boson transverse momentum spectrum caused by the finite top-quark mass, bottom-quark contributions, and electroweak gauge boson terms. All three effects act to decrease the Higgs boson transverse momentum distribution for observable momenta, with shifts reaching $\ensuremath{-}8%$ at the Tevatron and $\ensuremath{-}30%$ at the LHC. The shifts have a significant dependence on the Higgs ${p}_{T}$, and are especially important if large momenta are selected by experimental cuts.
Fractures and avascular necrosis before and after orthotopic liver transplantation: long-term follow-up and predictive factors.

With early posttransplant bone loss, orthotopic liver transplantation (OLT) recipients experience a high rate of fracturing and some avascular necrosis (AVN), but little is known about the incidence of and predictive factors for these skeletal complications. We studied 360 consecutive patients who underwent transplantation for primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) and assessed both vertebral and nonvertebral (rib, pelvic, and femur) fractures in a protocolized fashion. Before OLT, 20% of the patients had experienced fracturing, and 1.4% of the patients had experienced AVN. Following OLT, there was a sharp increase in fracturing, with a 30% cumulative incidence of fractures at 1 year and 46% at 8 years after transplantation. In contrast to previous studies, there was a similar incidence of posttransplant vertebral and nonvertebral fractures. The greatest risk factors for posttransplant fracturing were pretransplant fracturing and the severity of osteopenia and posttransplant glucocorticoids. Nine percent of the liver recipients experienced AVN after OLT, and this correlated with pretransplant and posttransplant lipid metabolism, bone disease (bone mineral density and fracturing), and posttransplant glucocorticoids. A novel association between cholestasis and AVN was also identified, the mechanism for which is not known. Conclusion: Fortunately, recent years have seen an increase in the bone mass of liver recipients and, along with this, less fracturing and less AVN. Nonetheless, 25% of patients undergoing OLT for chronic cholestatic liver disease still develop de novo fractures after OLT; this situation demands an ongoing search for effective therapeutic agents for these patients. (HEPATOLOGY 2007.)
Response of Low Seed Phytic Acid Soybeans to Increases in External Phosphorus Supply

Commercialization of soybean [Glycine max (L.) Merr.] varieties with low seed phytic acid will depend on the stability of the trait when grown in soils with a wide range of P availabilities and on the impact of altered P composition on seed protein and oil concentrations. Impacts of deficient (0.05 mmol L-1) to excessive (0.9 to 1.2 mmol L -1 ) levels of external P on seed P composition of normal and low phytic acid lines and of altered seed P composition on seed protein and oil synthesis were evaluated. Soybean lines homozygous recessive (pha/pha) at one of two loci with genes that condition the low seed phytic acid trait had the same greater-than-threefold increase in phytic acid in response to increasing external P as their normal phytic acid parent, 'AGS Prichard-RR' (Pha/Pha). This supports the conclusion from previous inheritance studies that the low seed phytic acid trait in CX1834-1-2 is controlled by epistatic interaction between two independent recessive genes. The seed phytic acid concentration in the low phytic acid line Q03PHY-443 (derived from CX1834-1-2) was <2 g phytic acid P kg -1 dry wt. when grown under deficient to excessive external P. As the P supply increased, seed inorganic P concentrations for this line increased from 0.8 to 4.0 g kg -1 dry wt., compared to an increase of 0.2 to 0.6 g kg -1 dry wt. for the normal phytic acid lines. Seed protein and oil concentrations did not differ significantly between normal and low phytic acid lines. These results support continued development of varieties with low seed phytic acid and high yields.
Some Mechanical Design and Construction Aspects of the MIT-LNS Linac

A high degree of RF phase stability, throughout a high-average-power, physically large, microwave system requires careful attention to the design of the mechanical joints, supports and anchors, and of the numerous branches of its widely dispersed heat transfer network. The major designs discussed are: the 180m long coaxial drive line supports, anchors and thermal enclosure (for ± 1° phase stability,), the rectangular and disk loaded waveguide heat transfer and mechanical support designs, and the two 190 1/s cooling water systems that are designed to maintain temperatures at 36 ± 0.9°C and 45 ± 0.1°C, respectively.