cssi/SciSciGPT-SciSciNet huggingface dataset:
Self-Organizing Networks for Nonparametric Regression

Widely known statistical and artificial neural network methods for regression are based on function approximation, i.e. representing an unknown (high-dimensional) function as a decomposition/superposition of simpler (low-dimensional) basis functions. Such methods naturally follow the supervised learning paradigm. In this paper we discuss a different approach to nonparametric regression that is based on unsupervised learning. Unsupervised learning methods are commonly used for modeling an (unknown) density distribution and for Vector Quantization. However, it can be also used for adaptive positioning of units (“knots”) along the regression surface, thereby providing discrete approximation of the unknown function. A method for adaptive positioning of knots called Constrained Topological Mapping(CTM) is discussed in detail. CTM is a modification of the biologically inspired method known as Kohonen’s Self-Organizing Maps (SOM) suitable for regression. SOM and CTM methods effectively combine iterative (flow through) computation and local regularization to achieve robust performance and modeling flexibility. This paper describes SOM/CTM methods in the general framework of adaptive methods for regression. We also suggest several statistically motivated improvements of these methods.
Heart sound classification via sparse coding

Introduction: The aim of the Physionet/CinC Challenge 2016 is to automatically classify heart sound recordings as normal or abnormal. The Challenge provides 3,153 labeled audio recordings taken from a single precordial location, as well as Springer's state-of-the-art beat segmentation algorithm. Algorithm: Using Springer's segmentation algorithm, we divide each audio segment into an array of sub-second audio files corresponding to the four phases of the cardiac cycle. We take an N-point FFT of each audio segment and create five different data matrices: one for each sub-cycle (S1, Systole, S2, and Diastole), and one for a complete cardiac cycle. A column of the data matrix corresponds to the N-point FFT of one audio segment. Using sparse coding, we decompose the data matrix into a dictionary matrix and a sparse coefficient matrix. The dictionary matrix represents statistically important spectral features of the audio segments. The sparse coefficient matrix is a mapping that represents which features are used by each segment. Working in the sparse domain, we train support vector machines (SVMs) for each sub-cycle and for the complete cycle. We train a sixth SVM to combine the results from the preliminary SVMs into a single binary label for the entire sound recording. Results: Our algorithm achieves a cross-validation score of 0.8652 (Se=0.8669 and Sp=0.8634). The best unofficial score when tested on a subset of the unknown challenge data is 0.812 (Se=0.825 and Sp=0.799). Conclusions: We developed an algorithm to classify heart sound recordings as normal or pathological. Our results show that sparse coding is an effective way to define spectral features of the cardiac cycle and its sub-cycles for the purpose of classification. Further work will attempt to increase the sensitivity and specificity of the algorithm by exploring other classifiers while still working in the sparse domain.
Nickel-Catalyzed Cross-Coupling of Vinyl Dioxanones to Form Enantiomerically Enriched Cyclopropanes

Under the conditions of nickel(0) catalysis, enantiomerically enriched vinyl dioxanones engage boroxines or B2(pin)2 in stereospecific cross-coupling to form diverse tetrasubstituted cyclopropanes bearing all-carbon quaternary stereocenters. The collective data corroborate a mechanism involving nickel(0)-mediated benzylic oxidative addition with inversion of stereochemistry followed by reversible olefin insertion to form a (cyclopropylcarbinyl)nickel complex, which upon reductive elimination releases the cyclopropane.
An Approximation Algorithm for the Fault Tolerant Metric FacilityLocation Problem

We consider a fault tolerant version of the metric facility location problem in which every city, j, is required to be connected to r j facilities. We give the first non-trivial approximation algorithm for this problem, having an approximation guarantee of 3 · H k , where k is the maximum requirement and H k is the kth harmonic number. Our algorithm is along the lines of [2] for the generalized Steiner network problem. It runs in phases, and each phase, using a generalization of the primal–dual algorithm of [5] for the metric facility location problem, reduces the maximum residual requirement by one.
Conduct, Affiliation, and Messages: A Typology of Statutes Addressing Political Deception

The second chapter of this project is an exploration of the statutes around the nation that address political deception. It is broken into three sections, which will explain the definition of the categories for the statutes and how some of the examples, found in the Appendix, fit into each one. This will be followed by a discussion of the constitutionality of these statutes. There will also be a brief discussion of punishments for political deception. The chapter concludes with an argument that while strong First Amendment protection of political speech is important, the legal arguments against these statutes creates a different set of problems.
Whole genome scan reveals the multigenic basis of recent tidal marsh adaptation in a sparrow

Natural selection acts on functional molecular variation to create local adaptation, the good fit we observe between an organism's phenotype and its environment. Genomic comparisons of lineages in the earliest stages of adaptive divergence have high power to reveal genes under natural selection because molecular signatures of selection on functional loci are maximally detectable when overall genomic divergence is low. We conducted a scan for local adaptation genes in the North American swamp sparrow (Melospiza georgiana), a species that includes geographically connected populations that are differentially adapted to freshwater vs. brackish tidal marshes. The brackish tidal marsh form has rapidly evolved tolerance for salinity, a deeper bill, and darker plumage since colonizing coastal habitats within the last 15,000 years. Despite their phenotypic differences, background genomic divergence between these populations is very low, rendering signatures of natural selection associated with this recent coastal adaptation highly detectable. We recovered a multigenic snapshot of ecological selection via a whole genome scan that revealed robust signatures of selection at 31 genes with functional connections to bill shape, plumage melanism and salt tolerance. As in Darwin's finches, BMP signaling appears responsible for changes in bill depth, a putative magic trait for ecological speciation. A signal of selection at BNC2, a melanocyte transcription factor responsible for human skin color saturation, implicates a shared genetic mechanism for sparrow plumage color and human skin tone. Genes for salinity tolerance constituted the majority of adaptive candidates identified in this genome scan (23/31) and included vasoconstriction hormones that can flexibly modify osmotic balance in tune with the tidal cycle by influencing both drinking behavior and kidney physiology. Other salt tolerance genes had potential pleiotropic effects on bill depth and melanism (6/31), offering a mechanistic explanation for why these traits have evolved together in coastal swamp sparrows, and in other organisms that have converged on the same salt marsh syndrome. As a set, these candidates capture the suite of physiological changes that coastal swamp sparrows have evolved in response to selection pressures exerted by a novel and challenging habitat.
Enrichment and Selection of Stem Cell-Derived Tissue-Specific Precursors

Human embryonic stem cells have the capacity for self-renewal and pluripotency, making them a primary candidate for tissue engineering and regenerative therapies. They also provide an opportunity to study the development of human tissues ex vivo. To date, numerous hESC lines have been developed and characterized. In this chapter, we will review the strategies used to direct tissue-specific differentiation of embryonic stem cells. We also will discuss how these strategies have produced new sources of tissue-specific progenitor cells. Finally, we will describe the next generation of methods being developed to identify and select stem cell-derived tissue precursors for experimental study and clinical use.
Proteomic Profiling and Target Identification in Lymphoma

This chapter provides an overview of the proteomic profiling strategies that are currently in use, including mass spectrometry, protein arrays, phosphoprotein profiling, and quantitative protein analysis techniques. Examples are discussed on how these technologies can be utilized for the identification of biologic targets in human malignant lymphomas.
Regulation of peptide hormone receptors and gonadal steroidogenesis.

Publisher Summary This chapter discusses regulation of peptide hormone receptors and gonadal steroidogenesis. The control of gonadal function by gonadotropins and prolactin is expressed through activation of plasma-membrane effector systems following hormone binding to specific, high-affinity receptors on the target-cell surface. Hormonal stimulation of characteristic gonadal responses by gonadotropins is predominately mediated by the adenylate cyclase protein kinase pathway, whereas the nature and mechanism of prolactin actions are less defined. Peptide hormones comprise one of the major groups of chemical signals by which intercellular communications operate within the organism. The low concentrations at which hormones circulate are commensurate with the high affinities of their cell-surface receptor sites, and the marked specificities of such receptors permit recognition of the circulating hormone amid a vast excess of other protein molecules. These well-defined binding properties of peptide receptors are similar to those of antigen-antibody reactions. In B lymphocytes, the immunoglobulin molecule serves as a surface receptor comparable to the peptide hormone receptor. The ability of peptide hormones to regulate the concentrations of their specific receptor sites in endocrine target cells is demonstrated in numerous tissues.
Abstract B18: Modeling renal medullary carcinomas identifies druggable vulnerabilities in SMARCB1-deficient cancers

Renal medullary carcinomas (RMCs) are thought to be driven by the loss of tumor suppressor, SMARCB1. These rare kidney cancers carry a very poor prognosis and primarily affect African American adolescents and young adults with sickle cell trait. From two patients with RMC, we have identified by whole-genome sequencing mechanisms of SMARCB1 loss (e.g., inactivating fusion events involving SMARCB1). We developed in vitro models of primary and relapsed metastatic disease. We performed biochemical and functional studies to conclusively show that RMC is dependent on loss of SMARCB1, similar to rhabdoid tumors and atypical teratoid/rhabdoid tumors. Furthermore, we performed small-molecule screens, pooled CRISPR-Cas9 knockout, and RNAi suppression screens focused on druggable cancer targets. Integration of these orthogonal methods identifies a core set of targets that may provide a rational approach to therapeutic targeting for this rare kidney cancer and other SMARCB1-deficient cancers. Citation Format: Andrew L. Hong, Yuen-Yi Tseng, Bryan D. Kynnap, Mihir B. Doshi, Jeremiah Wala, Gabriel Sandoval, Alanna J. Church, Elizabeth Mullen, Cigall Kadoch, Charles W.M. Roberts, Rameen Beroukhim, Jesse S. Boehm, William C. Hahn. Modeling renal medullary carcinomas identifies druggable vulnerabilities in SMARCB1-deficient cancers [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr B18.
Removing Outliers from 3D Macrotexture Data by Controlling False Discovery Rate

AbstractMeasurement of pavement macrotexture by noncontacting means is often contaminated by erroneous readings made by the instrument. These errors can be caused by extreme diffusion or refraction...
Values of cancer survivors and the supportive role of recreational video games.

Value-affirming activities have been linked to positive health outcomes and improved ability to cope. For cancer survivors who regularly play video games, might the games have potential to affirm v...
Adaptive dose-finding based on safety and feasibility in early-phase clinical trials of adoptive cell immunotherapy:

Background/aims:Dose feasibility is a challenge that may arise in the development of adoptive T cell therapies for cancer. In early-phase clinical trials, dose is quantified either by a fixed or pe...
Obesity is not associated with increased difficulty placing peripheral IVs in trauma activation patients.

Abstract Introduction Previous studies have identified obesity as a risk factor for difficult IV access, but this has not been studied in the acute trauma setting. The primary objective was to determine if obesity is associated with increased difficulty placing peripheral IVs in trauma patients. Secondary analysis evaluated IV difficulty and associations with nursing self-competence ratings, trauma experience, and patient demographics. Methods Prospective, observational study at academic level I trauma center with 58,000 annual visits. Trauma activation patients between January and October of 2016 were included. Each nurse who attempted IV placement, completed anonymous 7 question survey, including trauma experience (years), self-competence and IV difficulty (Likert scales 1–5), and attempts. Demographic and clinical information was retrospectively collected from the EMR and nursing surveys. Descriptive statistics, chi-square tests, and spearman correlations were used. Results 200 patients included in the study with 185 BMI calculations. 110 overweight (BMI > 25) and 48 obese (BMI > 30). 70 (35%) female, 149 (75%) white, average age 48. Increased BMI and IV difficulty displayed spearman correlation (ρ) of 0.026 (P = 0.72) suggesting against significant association. Increased trauma experience and self-competence ratings significantly correlated with decreased IV difficulty, ρ = −0.173 and −0.162 (P = 0.010 and 0.014). There was no statistically significant association with IV difficulty in regards to patient race, age, sex, or location of IV placement. Conclusion Obesity was not associated with increased difficulty in placing peripheral IVs in trauma activation patients. Nurses with greater trauma experience and higher self-competence ratings, had less difficulty inserting IVs.
An exploratory analysis of the latent structure of process data via action sequence autoencoders

Computer simulations have become a popular tool for assessing complex skills such as problem-solving. Log files of computer-based items record the human-computer interactive processes for each respondent in full. The response processes are very diverse, noisy, and of non-standard formats. Few generic methods have been developed to exploit the information contained in process data. In this paper we propose a method to extract latent variables from process data. The method utilizes a sequence-to-sequence autoencoder to compress response processes into standard numerical vectors. It does not require prior knowledge of the specific items and human-computer interaction patterns. The proposed method is applied to both simulated and real process data to demonstrate that the resulting latent variables extract useful information from the response processes.
Dermatologists' Perceptions and Use of Electronic Health Record Systems

Introduction: Electronic Health Records (EHR) have been adopted and integrated into medical practices over the past 20 years. Many positive and negative implications have been described by physicians using EHR. This study aims to US dermatologists' perceptions and use of EHR within their clinical practice. Methods: A validated survey was administered to US dermatologists at a national educational conference to assess use and perceptions of EHR. Results Seventy-two percent (291/400) of those sampled completed greater than 90% survey and were included in outcome analysis. Eighty-six percent of the participants were currently using or had used EHR. Most dermatologists felt that EHR negatively impacted their workflow efficiency and face-to-face time with patients. A portion of dermatologists thought that EHR improved their documentation. Limitations: Selection bias may have led those with strong beliefs with EHR more likely to complete the entire survey. Conclusion: Despite widespread adoption, most dermatologists have a negative impression of EHR and felt that it interfered with their ability to effectively see patients. Interventions to improve EHR should focus on improving workflow efficiency and maximizing the amount of time dermatologists can spend with patients.
Winkler, Adam. Beyond Bellotti, 32 Loy. L.A. L. Rev. 133 (1998)

Writing two decades after the Supreme Court of the United States held unconstitutional a ban on corporate political spending to influence ballot-initiative measures in First National Bank of Boston...
Professors of Natural Philosophy in the Nineteenth Century

The introductory physics course taught in American College and Universities in the twenty-first century is a descendent of the natural philosophy—later, physics—course that developed in these institutions in the nineteenth century. In the present paper, I discuss the backgrounds of a number of prominent professors of natural philosophy who taught these courses. These came, variously from experience as high-school teachers, engineers, and clergymen. Few of them planned to become faculty members, as contrasted to today’s professors who have rigorous educational and research training to prepare themselves for their task.
Translocation of neural crest cells within a hydrated collagen lattice

Chick neural tubes were cultured either on planar substrata of collagen-coated Falcon plastic in growth medium with serum or within a hydrated collagen lattice (HCL) in growth medium either with or without serum. Using time-lapse cinemicrography, neural crest cells were observed emigrating from neural tubes over the collagen substrata. Once separated from the neural tube, they seldom reunite with it. Though the average rate at which the neural crest cells translocate was the same in the different culture conditions, approximately 1.0 micron/min, distinct differences in morphology and mode of translocation were observed. Neural crest cells on collagen-coated culture dishes have a flattened fibroblastic morphology and mode of translocation; in an HCl with serum, they have a bipolar shape and translocate by advancing a long, narrow leading protrusion and by periodically retracting the attenuated trailing portion of the cell; and in a serum-free HCL, they have a unipolar shape and translocate by advancing a long, narrow, branched leading protrusion and by periodically transferring the cytoplasm of the large, rounded trailing cell body forward, past a bulbous structure, and into the leading protrusion.
3D transvenous radiofrequency ablation of manifest epicardial posterior-septal accessory pathways in children: Can technology innovations improve the outcome?

INTRODUCTION The aim of the study was to revise our more recent experience about epicardial posterior-septal accessory pathways radiofrequency transcatheter ablation in children and young patients using a transvenous approach through the coronary sinus, to understand if new mapping and ablation technologies can increase success rate and safety. METHODS AND RESULTS Twenty children (mean age 13 ± 3 years) with epicardial posterior-septal accessory pathways (14 in coronary sinus and 6 in the middle cardiac vein) underwent radiofrequency transcatheter ablation with CARTO-3® system with help of the CARTO-Univu® module. Acute success rate was 73%. No patient was lost to follow-up (mean time 11.4 ± 9 months). The recurrence rate was 19%. Two patients underwent a successful redo-procedure; the overall long-term success rate was 65%. Navistar® catheter presented the highest acute success rate in the coronary sinus. Navistar SmartTouch® was the only catheter that did not present recurrences after the acute success, and it was successfully used in two patients previously unsuccessfully treated with a Navistar ThermoCool®. Acute success rate was 79% without image integration with angio-CT, while it was 63% after the introduction of CARTO-Merge®. CONCLUSION Epicardial posterior-septal accessory pathways can be definitively eliminated by transvenous radiofrequency transcatheter ablation in more than half of the cases in children. Acute success rate does not seem to depend on catheters used, but contact-force catheter seems to be useful in cases with recurrences. Image integration with cardiac-CT does not increase success rate, but it is useful to detect coronary sinus alterations to better guide ablation strategy.
Multivalent Feedback Inhibition of Aspartokinase in Bacillus polymyxa I. KINETIC STUDIES

Abstract Aspartokinase, partially purified from extracts of Bacillus polymyxa, is inhibited by combinations of l-threonine and l-lysine at concentrations below 1 mm and by the amino acids separately at much higher concentrations. At 25°, the presence of the feedback inhibitors leads only to a decrease in the maximal velocity of the aspartokinase reaction. However, at 37° the affinity for l-aspartate is also markedly reduced by the inhibitors. Sigmoid substrate kinetics are not observed under any conditions. At 37°, but not at 25°, the apparent Km for l-aspartate is highly dependent on enzyme concentration, increasing from 0.4 mm to about 50 mm as the enzyme concentration is decreased from 13.4 to 0.17 units per ml. At 25°, the apparent Km for l-aspartate remains constant at about 1.5 mm over the same range of enzyme concentration. The presence of dioxane also leads to an increase in the apparent Km for l-aspartate, but at 25°, higher concentrations of the solvent are required to exert an effect than at 37°. It is suggested that at 37°, but not at 25°, the active form of aspartokinase dissociates into lower molecular weight units which have a markedly lower affinity for l-aspartate than the native enzyme.
Quantitative failure metric for gravity dams

Summary Quantitative failure monitoring is a critical tool for safety assessment of concrete dams. This includes damage occurrence, intensity, location, number, size, and propagation pattern. Such an assessment is essential for a quantifiable prioritization of repair and will thus reduce overall cost and improve safety. This paper will address this timely topic through the nonlinear transient analysis of a dam and failure will be ascertained through a multi-scale damage index. A damage-plastic model for mass concrete is used, Drucker-Prager elasto-plastic one for the foundation, and infinite elements are used for far-field boundaries. Water-dam interaction is accounted for through fluid finite elements. It is determined that the proposed damage indices can indeed provide a quantitative metric for the degree of failure in gravity dams in terms of the input dynamic motion. Copyright © 2014 John Wiley & Sons, Ltd.
Super chips for artificial intelligence

There is at least one field - artificial intelligence - that can effectively utilize air of the projected advances of semiconductor technology for the foreseeable future. The potential applications will be just as widespread, with education, health, industry, and service sectors among the many areas leading to a large demand for highly sophisticated solid state components. This address will assess these expanding virtues and their effect on the IC. Currently prevailing views about the future demand for high-powered computational elements are sometimes misguided. One such myth says that the demand for 32b (or larger) processors is likely to be limited because most applications do not need so much computational power. What these estimates fail to take into account are the computational needs of error-tolerance and user-friendliness that are essential if we expect ordinary mortals to use tomorrow's microcomputers effectively. The second myth stems from the view that a high powered LISP computer will be adequate to handle all of AI's computing needs. There are many topics that arise in AI for which the LISP machines alone are not adequate: perception problems for vision and speech, motor problems of manipulation and mobility in robotics, symbol manipulation problems of language, repetitive knowledge, recognition of rule-based inference in expert systems, combinatorial search in game playing and puzzle solving, massively parallel processing for instantaneous extraction and matching of relevant information from large knowledge bases. Each of these problems involves a wide variety of computational tasks, making it difficult to select any one architecture as the most desirable. A more probable AI architecture would be a multiprocessor structure with a large number of asymmetric processing elements sharing a large knowledge base. Furthermore, the trend from VLSI to ULSI will be towards higher degrees of Integration leading to higher functionality. A million-element chip might include functions currently requiring four or five chips. CPU, virtual memory, floating point arithmetic, array processor and cache. A hundred-million element chip might contain a 100 processor system with a common bus to a larger external shared memory. It is important to note that all of the hundred processors need not be identical. Processing elements should have dynamically alterable PLAs, leading to tailored architectures for different computational tasks. A billion-element super-chip might provide a 100 megabyte common memory and 100 processing elements on a single chip, along with A/D and D/A and networking interfaces. Even a super chip could barely perform many of these AI problems. A review of the foregoing problems illustrates the need for flexible and powerful computational elements in the future. It is indeed possible that we can haven billion element super chip by the turn of the century: it is interesting to speculate how we might use it!
Iconicity in American sign language: concrete and metaphorical applications

American Sign Language (ASL) describes spatial information (e.g., shapes, configurations, movement and location of figures in space) through a productive system of iconic ``classifier'' predicates. Many lexical items denoting concrete objects or actions are derived from the classifier systems many lexical items and non-lexicalized descriptions of abstract objects or actions are derived from the classifier system as well, through metaphorical mappings from the spatial domain to abstract domains. Starting from the ASL data, this paper presents an ``analogue-building'' model of the creation of iconic forms, which can cover spoken-language as well as sign-language iconicity, and a ``double mapping'' analysis of metaphorical iconicity. The double mapping analysis is supported by the existence of signs that share a metaphorical mapping but not an iconic mapping. The data and analyses presented here underscore the importance of space in conceptualizing non-spatial domains.
Chemical Nature of Malty Flavor and Aroma Produced by Streptococcus lactis var. maltigenes

Mature skim milk cultures of Streptococcus lactis var. maltigenes were steam distilled at low temperature under reduced pressure. Ethyl ether extracts were prepared from the distillates and analyzed by gas-liquid chromatography and mass spectrometry. Twenty of 31 components detected in the culture distillates were identified positively and 11 tentatively, whereas 10 of 19 components detected in the heated skim milk control were identified positively and 9 tentatively. Among components detected in the culture distillate, but not detected in the heated skim milk distillate, and which have not been previously identified in milk cultures of the organism were phenylacetaldehyde and phenethanol. Quantitative analyses of the volatiles entrained from milk cultures of several strains of S. lactis var. maltigenes revealed a probable relationship between variation in the character of the aroma of the cultures and the alcohol/aldehyde ratio.
The Relationship between Reinforcing Effects and in Vitro Effects of D1 Agonists in Monkeys

The reinforcing effects of many psychomotor stimulants have been related to increased dopaminergic neurotransmission and stimulation of central nervous system (CNS) dopamine (DA) receptors. Consistent with this notion, some drugs that directly stimulate DA receptors have been found to function as positive reinforcers. The present experiments were designed to examine why some, but not all, D1 receptor agonists can function as reinforcers in rhesus monkeys by comparing behavioral and CNS in vitro measures of potency and efficacy. Seven rhesus monkeys were allowed to self-administer cocaine under a progressive-ratio (PR) schedule until stable responding was established. Various doses of D1 agonists, previously reported to function as positive reinforcers, were then made available for self-administration. Stimulation of cAMP production in rhesus and rat striatal tissue was studied for these compounds and for D1 agonists previously reported not to function as positive reinforcers in monkeys (SKF 38393, SKF 77434 and S (−)-6-BrAPB). Blockade of DA uptake in rat striata was also examined for all compounds. SKF 81297, SKF 82958 and R (+)-6-BrAPB maintained responding under the PR schedule and did not differ significantly in efficacy as positive reinforcers; SKF 81297 was less potent than the other two agonists. SKF 81297, SKF 82958 and R (+)-6-BrAPB stimulated higher levels of cAMP production in rhesus striata than did SKF 38393, SKF 77434 and S (−)-6-BrAPB. In contrast, all compounds blocked DA uptake. Thus, reinforcing efficacy among D1 agonists increases with efficacy in stimulating D1 receptors.
Hexim-1 modulates androgen receptor and the TGF-β signaling during the progression of prostate cancer.

BACKGROUND Androgen and TGF-β signaling are important components during the progression of prostate cancer. However, whether common molecular events participate in the activation of these signaling pathways are less understood. METHOD Hexim 1 expression was detected by immunohistochemistry of human tissue microarrays and TRAMP mouse models. The in vivo significance of Hexim-1 was established by crossing the TRAMP mouse model of prostate cancer with Hexim-1 heterozygous mice. TRAMP C2 cell line was also modified to delete one copy of Hexim-1 gene to generate TRAMP-C2-Hexim-1+/− cell lines. RESULTS In this report, we observed that Hexim-1 protein expression is absent in normal prostate but highly expressed in adenocarcinoma of the prostate and a characteristic sub-cellular distribution among normal, benign hyperplasia, and adenocarcinoma of the prostate. Heterozygosity of the Hexim-1 gene in the prostate cancer mice model and the TRAMP-C2 cell line, leads to increased Cdk9-dependent serine phosphorylation on protein targets such as the androgen receptor (AR) and the TGF-β-dependent downstream transcription factors, such as the SMAD proteins. CONCLUSION Our results suggest that changes in the Hexim-1 protein expression and cellular distribution significantly influences the AR activation and the TGF-β signaling. Thus, Hexim-1 is likely to play a significant role in prostate cancer progression. Prostate 72:1035–1044, 2012. © 2011 Wiley Periodicals, Inc.
Strong coupling expansions for nonintegrable hamiltonian systems

Abstract We present a method for studying nonintegrable Hamiltonian systems H(I,θ) = H0(I) + kH1(I,θ) (I, θ are action-angle variables) in the regime of large k. Our central tool is the conditional probability P(I,θ,t | I0,θ0,t0) that the system is at I. θ at time t given that it resided at I0, θ0 at t0. An integral representation is given for this conditional probability. By discretizing the Hamiltonian equations of motion in small time steps, ϵ, we arrive at a phase volume-preserving mapping which replaces the actual flow. When the motion on the energy surface E = H(I,θ) is bounded we are able to evaluate physical quantities of interest for large k and fixed ϵ. We also discuss the representation of P (I,θ,t | I0,θ0t0) when an external random forcing is added in order to smooth the singular functions associated with the deterministic flow. Explicit calculations of a “diffusion” coefficient are given for a non-integrable system with two degrees of freedom. The limit ϵ → 0, which returns us to the actual flow, is subtle and is discussed.
Multiphoton imaging for deep tissue penetration and clinical endoscopy

In this paper, we present our efforts in improving the penetration depth of MPM and the development of a multiphoton endoscope for imaging intrinsic tissue fluorescence and harmonic generation in vivo, with a main focus on instrument design and optimization.
Stochastic theory for the kinetics of migration of ligands in biomolecules.

Abstract A stochastic approach in terms of master equations with linear and nonlinear transition rates for the dynamics of the migration of ligands in biomolecules is presented. Coupling to a bath with constant ligand concentration as well as multiple occupancies by ligands of certain sites inside the biomolecule are allowed. Explicit expressions for the fraction of biomolecules that have not bound a ligand at time t under experimental constraints λ are found by solving the generating function of the probability obeying the master equation. For highly non-linear systems a computer oriented procedure is presented. The validity of a description with a system of coupled linear deterministic equations is discussed. Relevance to experimental data and applications to other biophysical systems are outlined.
X-Ray Attenuation Cross Sections for Energies 100 eV to 100 keV and Elements Z = 1 to Z = 92

This work presents for the energy range 0.1--100 keV the National Bureau of Standards (NBS) database of experimental x-ray attenuation coefficients (total absorption cross sections) and cross sections calculated using a relativistic Hartree--Slater model for the photoelectric cross section for all elements of atomic number Z = 1--92. The information is displayed in both tabular and graphical form. Also shown on the graphs are cross sections obtained using the semiempirical set of recommended values of B. L. Henke and co-workers (Atomic Data and Nuclear Data Tables 27, 1 (1982)). A bibliography of the NBS database for this energy range is included. copyright 1988 Academic Press, Inc.
Electron-electron relaxation in heterostructures

Stimulated by recent data for the electron-electron relaxation time measured in two different double-quantum-well systems we consider both intralayer and interlayer screened electron-electron interactions and include a contribution beyond the simple golden-rule result. In particular, we find that (i) including a nongolden-rule contribution of the same order in the interaction always reduces the rate, (ii) as a result, our intralayer golden-rule contribution is significantly smaller than all published calculations, and (iii) while including interlayer scattering may increase the rate, it is still less than the measured rate in a wide double-quantum-well system.
Hypnosis as an adjunct to thought-stopping and covert reinforcement in the treatment of homicidal obsessions in a twelve-year-old boy

Abstract A combined cognitive behavioral approach was used to successfully treat matricidal obsessions in an otherwise psychologically well-adjusted 12-year-old boy. The primary problem was conceptualized as anxiety over loss of control. Therapeutic techniques included re-defining of symptoms, thought-stopping, hypnotic enhancement of imagery in order to facilitate cognitive restructuring, covert reinforcement, home practice, and paradoxical instructions to produce the symptom. A decline in obsessions began after 3 sessions and total remission was observed after 6 sessions (10 weeks). 2-year follow-up revealed no recurrence of symptoms. The value of hypnosis as an adjunct to behavior therapy with children is discussed.
Tradition and innovation. Paul Ricoeur and the dynamics of critical theology

Using the philosophy of Paul Ricoeur as an interpretive matrix, this article suggests that critical theologies may be understood as an instantiation of the concrete unity of past and present in religious symbol. The intransigence of debates between critical and counter-critical theologies is thus disclosed as an inability to account for and remain within the past-future dynamic in religious symbol. Ricoeur’s Freud and Philosophy provides the philosophical terminology for unpacking the simultaneously archaeological and teleological character of symbol. The article then turns to Ricoeur’s accounts of metaphor and narrative to make the following observations: (1) Reflecting the metaphorical capacity of language, critical theologies occur as a juxtaposition of known and unknown, here understood as a juxtaposition of past and present in religious expression; (2) The inherently tensive character in critical theology gives way to a dialogical trajectory. Critical theologians engender Ricoeur’s reference to the p...
Neurog3 gene dosage regulates allocation of endocrine and exocrine cell fates in the developing mouse pancreas

The basic helix-loop-helix transcription factor Neurog3 (Neurogenin3 or Ngn3) actively drives endodermal progenitor cells towards endocrine islet cell differentiation during embryogenesis. Here, we manipulate Neurog3 expression levels in endocrine progenitor cells without altering its expression pattern using heterozygosity and a hypomorph. Lowered Neurog3 gene dosage in the developing pancreatic epithelium reduces the overall production of endocrine islet cells without significantly affecting the proportions of various islet cell types that do form. A reduced Neurog3 production level in the endocrine-directed pancreatic progenitor population activates the expression of Neurog3 in an increased number of epithelial progenitors. Yet a significant number of these Neurog3+ cells detected in heterozygous and hypomorphic pancreata, possibly those that express low levels of Neurog3, move on to adopt pancreatic ductal or acinar fates. These data directly demonstrate that achieving high levels of Neurog3 expression is a critical step for endocrine commitment from multipotent pancreatic progenitors. These findings also suggest that a high level of Neurog3 expression could mediate lateral inhibition or other unknown feedback mechanisms to regulate the number of cells that initiate Neurog3 transcription and protein production. The control of Neurog3+ cell number and the Neurog3 threshold-dependent endocrine differentiation mechanism combine to select a specific proportion of pancreatic progenitor cells to adopt the islet cell fate.
Early stages of axonal regeneration in the goldfish optic tract: an electron microscopic study.

Two hours after the goldfish optic tract was cut, the severed axons in the retinal stump of the tract showed ballooning of the axoplasm and myelin sheath in the region of the cut, with accumulation in the swollen axon of various organelles, including dense cored vesicles. By day 1 the myelin sheath had degenerated back to a node of Ranvier and the tip of the severed axon had formed a myelin-free terminal bulb with a well-organized core of 9–10 nm filaments. By 2 days, such terminal bulbs were often seen to be extended on a neck of cytoplasm a few micrometers in length, presumably indicating axonal outgrowth. In addition, occasional small bundles of axon sprouts were first seen at this time. The sprouts had a diameter of about 2 μm and contained a central core of 9–10 nm filaments surrounded by a mantle of cell organelles (smooth endoplasmic reticulum, mitochondria and diverse vesicles), with few if any microtubules. Sprouts within a bundle were separated by fairly uniform 10–15 nm spaces. Beginning at 3 days, significant numbers of microtubules appeared in the sprouts, and there was an increasing proportion of small diameter (⩾0.3 μm) sprouts. Thus it was not until 3 days that the sprouts took on the appearance usually considered to be typical of regenerating axons. By 6 days a dense layer of glial cells or macrophages formed a cap over the cut surface of the tract. Penetrating this layer were bundles containing up to 20–30 axon sprouts and also single axons which may have been serving as ‘pioneering’ fibres to which later-emerging axons would attach. There was no evidence that the regenerating axons were guided by the glial cells. At 6 days astroglia began to separate individual axons within the bundles but oligodendrocytes were still inactive at this time.
Arabidopsis Orthologs of Maize Chloroplast Splicing Factors Promote Splicing of Orthologous and Species-Specific Group II Introns

Chloroplast genomes in plants and green algae contain numerous group II introns, large ribozymes that splice via the same chemical steps as spliceosome-mediated splicing in the nucleus. Most chloroplast group II introns are degenerate, requiring interaction with nucleus-encoded proteins to splice in vivo. Genetic approaches in maize (Zea mays) and Chlamydomonas reinhardtii have elucidated distinct sets of proteins that assemble with chloroplast group II introns and facilitate splicing. Little information is available, however, concerning these processes in Arabidopsis (Arabidopsis thaliana). To determine whether the paucity of data concerning chloroplast splicing factors in Arabidopsis reflects a fundamental difference between protein-facilitated group II splicing in monocot and dicot plants, we examined the mutant phenotypes associated with T-DNA insertions in Arabidopsis genes encoding orthologs of the maize chloroplast splicing factors CRS1, CAF1, and CAF2 (AtCRS1, AtCAF1, and AtCAF2). We show that the splicing functions and intron specificities of these proteins are largely conserved between maize and Arabidopsis, indicating that these proteins were recruited to promote the splicing of plastid group II introns prior to the divergence of monocot and dicot plants. We show further that AtCAF1 promotes the splicing of two group II introns, rpoC1 and clpP-intron 1, that are found in Arabidopsis but not in maize; AtCAF1 is the first splicing factor described for these introns. Finally, we show that a strong AtCAF2 allele conditions an embryo-lethal phenotype, adding to the body of data suggesting that cell viability is more sensitive to the loss of plastid translation in Arabidopsis than in maize.
The sequences of hypF, hypC and hypD complete the hyp gene cluster required for hydrogenase activity in Bradyrhizobium japonicum

Abstract A region of DNA 6 kb downstream of the hydrogenase (H2ase) structural genes and directly downstream of the hypB gene of Bradyrhizobium japonicum was shown by mutational analysis to be necessary for H2ase synthesis. Sequencing of this region revealed two complete open reading frames, and the 5′ fragment of a third ORF. They encode proteins with homologies to the HypF, HypC and the N-terminus of HypD from other H2ase-containing organisms. The hypF of B. japonicum encodes a 753-aa protein with a predicted molecular mass of 80.3 kDa that contains the two zinc-finger motifs characteristic of other HypF proteins. The hypC encodes a 85-aa protein with a predicted molecular mass of 8.4 kDa. The 5′ portion of hypD, which encodes the first 35 aa, upon combining with the previously reported C-terminus of HypD, designated HypD′ ( Van Soom et al. (1993) Mol. Gen. Genet. 239, 235–240) encodes a protein with a predicted molecular mass of 42.4 kDa. Complementation studies on a H2 uptake defective strain of B. japonicum containing a polar mutation in the hyp operon revealed that the products of the hyp F, C, D, E genes are required for H2ase production. Evidence is also presented that the hyp genes are co-transcribed from a large operon together with the downstream genes hupGHIJK, making a polycistronic message of 11 genes.
Immunohistochemical detection of XIAP in mesothelium and mesothelial lesions

We examined benign and malignant mesothelial tissue samples for the presence of X-linked inhibitor of apoptosis protein (XIAP), a potent constituent of the inhibitor of apoptosis family of caspase inhibitors. We subjected 55 sections (31 malignant mesotheliomas, 2 well-differentiated peritoneal mesotheliomas, 13 pleural mesothelial hyperplasias, and 9 benign mesothelial tissues) from archival formalin-fixed, paraffin-embedded surgical tissue blocks to citrate-based antigen retrieval and then incubated them with monoclonal anti-XIAP (clone 48, dilution 1:250; BD Biosciences, San Jose, CA) at 4 degrees C for 72 hours and developed them using EnVision-Plus reagents (DAKO, Carpinteria, CA) and diaminobenzidine as the chromogen. Particulate or nonhomogeneous cytoplasmic staining was considered positive. All 9 normal mesothelial samples were negative for XIAP. Of 13 mesothelial hyperplasias, 1 (8%) was weakly positive in fewer than 10% of cells, as was 1 of 2 well-differentiated peritoneal mesotheliomas. Of 31 malignant mesotheliomas, 25 (81%) displayed XIAP positivity. XIAP immunostaining, when strong, allows for distinction of malignant from benign and hyperplastic mesothelial cell populations and is a potentially useful immunodiagnostic marker in small samples and morphologically controversial cases. Elevated expression of XIAP could contribute to tumorigenesis in mesothelioma.
The migration response to the economic turnaround in New England.

This paper is an investigation of the dynamics of interstate migration flows to and from New England since 1975. The main goal of the research is to study the timing and volume of the lagged migration adjustment to the regional economic turnaround and the temporal stability of patterns of regional inflows and outflows. The paper is an examination of the responsiveness of interstate migration to changing regional economic conditions based on annual interstate migration data and a set of cross-sectional destination-specific Poisson regression models. The results of the analysis add to our understanding of the economic revival in New England and the prospects for longer term employment growth in the region. Our knowledge of migration response and the regional labor-market adjustment process in general is also furthered.
Pediatric Concussions in United States Emergency Departments in the Years 2002 to 2006

Objectives To estimate the incidence and demographics of concussions in children coming to emergency departments (EDs) in the United States and describe the rates of neuroimaging and follow-up instructions in these patients. Study design This is a cross-sectional study of children 0 to 19 years old diagnosed with concussion from the National Hospital Ambulatory Medical Care Survey. National Hospital Ambulatory Medical Care Survey collects data on approximately 25 000 visits annually to 600 randomly selected hospital emergency and outpatient departments. We examined visits to United States emergency departments between 2002 and 2006. Simple descriptive statistics were used. Results Of the 50 835 pediatric visits in the 5-year sample, 230 observations, representing 144 000 visits annually, were for concussions. Sixty-nine percent of concussion visits were by males. Thirty percent were sports-related. Sixty-nine percent of patients diagnosed with a concussion had head imaging. Twenty-eight percent of patients were discharged without specific instructions to follow-up with an outpatient provider for further treatment. Conclusions Approximately 144 000 pediatric patients present to emergency departments each year with a concussion. Most of these patients undergo computed tomography of the head, and nearly one-third are discharged without specific instructions to follow-up with an outpatient provider for further treatment.