cssi/SciSciGPT-SciSciNet huggingface dataset:
Phe(13),Tyr(19)-melanin-concentration hormone and the blood-brain barrier: role of protein binding

Melanin-concentrating hormone (MCH), found both peripherally and centrally, is involved in food ingestion. Although its expression in brain is increased by fasting, it is not known whether it crosses the blood-brain barrier (BBB). Use of the sensitive method of multiple-time regression analysis has shown that almost all of the peptides and polypeptides tested cross the BBB at a rate faster than the vascular marker albumin. With this same method, however, we found that the 19-amino acid 125I-Phe13,Tyr19-MCH did not cross faster than 99mTc-albumin. Several mechanisms were excluded as possible explanations for the slow rate of influx. These included degradation, association with capillary endothelial cells, and transport from brain to blood. When Phe13,Tyr19-MCH was perfused in blood-free buffer, however, it entered the brain significantly faster than albumin. This suggested protein binding as an explanation for the slow rate of influx when the MCH was administered in blood. Protein binding was confirmed by capillary zone electrophoresis, which showed that almost all of the Phe13,Tyr19-MCH added to blood migrated with a large-molecular-weight substance. Sodium dodecyl sulfate-capillary gel electrophoresis of Phe13,Tyr19-MCH in buffer additionally showed that the MCH aggregated as a trimer, a factor not preventing its influx by blood-free perfusion. Thus, the results show that blood-borne Phe13,Tyr19-MCH does not significantly cross the BBB, probably because of its binding to serum proteins.
Why Read about the Old Masters

Categories and Classifications: Maussian Reflections on the Social. N. J. Allen. Methodology and History in Anthropology, vol. 6. David Parkin, series ed. New York: Berghahn Books, 2001. 172 pp. Durkheim Reconsidered. Susan Stedman Jones. Oxford: Polity, 2001. 288 pp.
Role of focal adhesion kinase in oocyte-follicle communication

Germ cells require communication with associated somatic cells for normal gametogenesis as exemplified by the oocyte which interacts with granulosa cells via paracrine factors as well as gap junctions located at sites of contact between these two cell types. The objective of the present study was to define the mechanisms by which cell-cell contact with the oocyte is controlled and determine the extent to which the oocyte actively participates in this association. Focal adhesion kinase (PTK2) was found to be activated at sites of contact between the oocyte and trans-zonal cell processes from the surrounding granulosa cells. In order to determine the functional significance of oocyte-derived PTK2 signaling in oocyte-follicle communication, an oocyte-specific ptk2 knockout was produced through a breeding strategy pairing a floxed ptk2-CAT-eGFP mouse with the Zp3-cre line. Since ptk2-null mice never develop to birth, this represents the first opportunity to define the role of ptk2 in oocytefollicle communication. Ablation of ptk2 within the developing oocyte resulted in lower fertility with reduced numbers of pups, lower rates of blastocyst formation, and reduced cell numbers per blastocyst. Follicles containing ptk2-null oocytes exhibited reduced oocyte diameter, reduced numbers of connexin 37 and 43 foci at the oocyte surface, and impaired dye coupling between oocyte and granulosa cells. These findings are consistent with a model in which PTK2 plays a critical role in establishing or maintaining oocyte-granulosa cell contacts that are essential for gap junction - mediated communication between granulosa cells and the oocyte.
A mini-electrodialysis system for desalting small volume saline samples for Fourier transform ion cyclotron resonance mass spectrometry

An affordable, commercially available mini-electrodialysis (mini-ED) system has been evaluated for the efficient desalting of small volume samples of seawater before analysis by electrospray Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS). Mini-ED FT-ICR mass spectra were compared with spectra for samples that were treated by C18 solid phase extraction, a commonly used method for rapid sample preparation for this type of analysis. In this comparison, it is clear that mini-ED provides more representative molecular information, compared with C18 isolation, and recovers the overwhelming majority of peaks from salt-free samples, indicating that it adequately represents the DOM that can be ionized and analyzed by ESI FT-ICR MS. The ED system produces a significant carbon blank. However, the substances contributing to this blank are not detectable by ESI FT-ICR MS. Based on these findings mini-ED is recommended as a promising method for the desalting of aqueous environmental samples before analysis by ESI FT-ICR MS.
Uncertainty in Life Cycle Assessment of Nanomaterials

Despite concerns regarding environmental fate and toxicology, engineered nanostructured material manufacturing is expanding at an increasingly rapid pace. In particular, the unique properties of single walled carbon nanotubes (SWCNT) have made them attractive in many areas, including high-tech power applications such as experimental batteries, fuel cells or electrical wiring. The intensity of research interest in SWCNT has raised questions regarding the life cycle environmental impact of nanotechnologies, including assessment of: worker and consumer safety, greenhouse gas emissions, toxicological risks associated with production or product emissions and the disposition of nanoproducts at end of life. However, development of appropriate nanotechnology assessment tools has lagged progress in the nanotechnologies themselves. In particular, current approaches to life cycle assessment (LCA) — originally developed for application in mature manufacturing industries such as automobiles and chemicals — suffer from several shortcomings that make applicability to nanotechnologies problematic. Among these are uncertainties related to the variability of material properties, toxicity and risk, technology performance in the use phase, nanomaterial degradation and change during the product life cycle and the impact assessment stage of LCA. This chapter expounds upon the unique challenges presented by nanomaterials in general, specifies sources of uncertainty and variability in LCA of SWCNT for use in electric and hybrid vehicle batteries and makes recommendations for modeling and decision-making using LCA in a multi-criteria decision analysis framework under conditions of high uncertainty.1
Chemistry of molecular clouds

A discussion is presented of the chemistry of quiescent molecular clouds, and the effects of the presence of polycyclic aromatic hydrocarbon molecules and of cosmic-ray induced ultraviolet photons are examined. A comparison is made with the chemistry occurring in molecular clouds that are subjected to shocks and the differences between dissociative and non-dissociative shocks are described. The changes in composition caused by intense cosmic ray fluxes or intense ultraviolet radiation fields are explored.
A VISIBLE ALLELE OF THE MUSCLE GENE sup-10 X OF C. ELEGANS

In this paper, we extend our previous analyses of a set of genes in Caenorhabditis elegans that are involved in muscle structure and function: unc-93 III, sup-9 II, sup-10 X and sup-11 I. We describe an unusual, visible allele of sup-10, examine how this allele interacts genetically with mutations in other genes of this set and propose that the wild-type products of the unc-93 and sup-10 loci may be components of a protein complex. We also describe a new gene of this set, sup-18 III, and the interaction of sup-18 alleles with mutations in the other genes.
A geometric approach to real time pitch detection

An approach to time-domain pitch detection based on the concepts of center of mass is presented and evaluated. Excursions, or bumps, in speech signals are treated as geometric areas and replaced by their total mass lumped at the centers of mass. Intervals between masses are grouped into candidate classes. Coincidence and coherence indices of these classes are computed to determine the most likely pitch estimate. Postprocessing consists of a simple error-correction and silence-detection scheme. This algorithm compares favourably in performance with the autocorrelation method, using pitch contours from electroglottograph signals as a reference. The algorithm is tested in noisy environments simulated by uniformly distributed white noise and multitalker babble noise. Results show that the algorithm is robust and accurate. The implementation of this algorithm for a vibrotactile device to aid lipreading is described. >
Caffeine-induced ulcerogenesis in the rat.

The present investigation has demonstrated that administration of caffeine alkaloid (6.25 mg/kg, 25 mg/kg, and 100 mg/kg) by stomach tube induces acute gastric ulcers in the fundus, pylorus, and antrum of fasting male and female rats. The ulcers are histologically characterized as superficial erosions of the glandular mucosa. Statistical evaluation of ulcer indices indicated a linear, log dose–response relationship for caffeine alkaloid, and a similar ulcerogenic effect in both male and female rats.
Demonstration of an ultra-stable temperature platform

We report on a new thermometer design and precision heater controller for use in cryogenic experiments near 2.2 K. The thermometer design reduces the thermal resistance between the thermometer and the liquid 4He sample to the point where the noise is limited by thermally driven electrical current fluctuations in the PdMn. The heater controller uses a series array of rf-biased Josephson junctions on a constant voltage state to precisely control the voltage drop across the heater resistor. This technology may be used to create a blackbody reference device with unprecedented stability.
SOLUBLE HLA IN TYPE I DIABETES. † 543

Class I Major Histocompatibility Complex (MHC) antigens are prominently expressed on the cell membranes of most nucleated cells; however, soluble form(S-HLA-I) has been described in serum or plasma, and may play a role in immunomodulation or autoimmune disease pathogenesis. To analyze the possible genetic relationship between S-HLA-I levels with MHC alleles in Type I diabetes, we studied the expression of S-HLA-I in the serum of 12 Caucasian patients with Type I diabetes, their 36 unaffected family members and 82 Caucasian individuals with known HLA phenotypes using a solid phase ELISA assay. Serum HLA-I concentrations were significantly higher in patients with Type I diabetes (mean=483 ng/ml) or their blood relatives (mean=424 ng/ml), compared to those values observed in normal controls (mean=241 ng/ml). There was no significant difference in S-HLA-I secretion in terms of the duration of diabetes; however, the stage of “honeymoom” periods were remarkedly longer in those patients who had the high S-HLA-I secretor status(n = 5, mean=812 ng/ml) and shorter in those diabetic patients who showed low S-HLA-I secretion (n = 7, mean=247 ng/ml).
Square Root and Perturbed Observation Ensemble Generation Techniques in Kalman and Quadratic Ensemble Filtering Algorithms

AbstractThe main goal of this work is to present a new square root ensemble generation technique that is consistent with a recently developed extension of Kalman-based linear regression algorithms such that they may perform nonlinear polynomial regression (i.e., includes a quadratically nonlinear term in the mean update equation) and that is applicable to ensemble data assimilation in the geosciences. Along the way the authors present a unification of the theories of square root and perturbed observation (sometimes referred to as stochastic) ensemble generation in data assimilation algorithms configured to perform both linear (Kalman) regression as well as quadratic nonlinear regression. The performance of linear and nonlinear regression algorithms with both ensemble generation techniques is explored in the three-variable Lorenz model as well as in a nonlinear model configured to simulate shear layer instabilities.
Human Embryonic Stem Cell-Derived Dopaminergic Neurons Reverse Functional Deficit in Parkinsonian Rats

We show that human embryonic stem cell-derived dopaminergic neurons survived transplantation to the neurotoxin 6-hydroxydopamine-lesioned rat striatum and, in combination with the cells newly differentiated from their progenitors, contributed to locomotive function recovery at 5 months. The animal behavioral improvement was correlated with the dopamine neurons present in the graft. Although the donor cells contained forebrain and midbrain dopamine neurons, the dopamine neurons present in the graft mainly exhibited a midbrain, or nigra, phenotype, suggesting the importance of midbrain dopamine neurons in functional repair. Furthermore, progenies of grafted cells were neurons and glia with greatly diminished mitotic activity by 5 months. Thus, the in vitro-produced human dopamine neurons can functionally engraft in the brain.
Unit based procedures: impact on the incidence of nosocomial infections in the newborn intensive care unit

Abstract Nosocomial infections are one of the major causes of morbidity in the Newborn Intensive Care Unit (NICU). Known risk factors include birth weight, gestational age, severity of illness and its related length of stay, and instrumentation. Infections result in prolonged hospital stays and, consequently, increased hospital costs. As advances in medical technology improve mortality in the tiniest of infants, it is imperative that health care providers identify effective interventions to minimize the risks of nosocomial infections in the NICU. This article examines the effects of common procedures on the incidence of nosocomial infections. Unit-based procedures discussed include visitation, hand washing and nail care, skin and cord care, maintenance of hubs in peripheral and central lines, gowning and isolation procedures, use and misuse of antibiotics, and unit design and staffing. Investigation of these procedures in individual units may reveal areas to improve patient outcomes.
Effect of Silver Coating on Barium Titanium Oxide Nanoparticle Toxicity.

Nanoparticles are presently being studied for optical and biomedical applications such as medical imaging and drug delivery. Nanoparticles impact the cellular environment due to many variables such as size, shape, and composition. How these factors affect cell viability is not fully understood. The purpose of this study is to test the toxicity effects of silver coating (Ag@) Barium Titanium Oxide (BaTiO3) nanoparticles on Rhesus Monkey Retinal Endothelial cells (RhRECs) in culture. The addition of silver to the nanoparticles increases their nonlinear optical properties significantly, making the Ag@BaTiO3 nanoparticles good candidates for nonlinear microscopy contrast agents. We hypothesize that by silver coating nanoparticles, there will be an increase in cell viability at higher concentrations when compared to non-silver coated nanoparticles. RhRECs were treated with BaTiO3 and Ag@BaTiO3 at concentrations of 0, 1.0, 10.0, and 100μg/ml for 24 hours at 370C + 5%CO2. After 24 hour incubation with respective nanoparticles, cell viability was determined using the trypan blue dye-exclusion method. Treatment with 0, 1.0 and 10.0μg/ml of Ag@BaTiO3 had minimal effect on cell viability, with 90% viable cells remaining at the end of the 24 hours treatment period. However, cells treated with 100μg/ml of Ag@BaTiO3 resulted in a decrease to 51% viable cells. Comparatively, cells treated with 0, 1.0 and 10μg/ml of BaTiO3 had no significant effect on cell viability (90% viable cells after treatment) while the 100μg/ml treatment resulted in a decrease to 29% viable cells. These results show that silver coating of BaTiO3 nanoparticles has a protective effect on cellular toxicity at high concentrations.
Rheumatoid vasculitis: diagnostic and therapeutic decisions

Rheumatoid vasculitis is an uncommon but potentially catastrophic complication of RA. There are few extensive experiences recorded in the current literature and there is no consensus regarding the clinical features, laboratory findings, histologic pattern, prognosis, or appropriate management of this syndrome. We therefore surveyed 1,947 North American ARA members for their perceptions of rheumatoid vasculitis. Four hundred twenty-eight surveys were returned, of which 290 were suitable for analysis. The majority of respondents were within 10 years of fellowships and were evenly distributed among private practice, and part-time and full-time academic positions. The respondents saw 15-50 rheumatoid arthritis (RA) patients weekly and less than five RA vasculitis patients annually. The majority correctly diagnosed two actual and complex case histories from patients with and without autopsy-proven vasculitis. Respondents associated the following features most strongly with rheumatoid vasculitis - mononeuritis multiplex, digital gangrene, digital ischemic lesions, nailfold ischemic lesions, non-healing leg ulcers, palpable purpura, fingertip nodules, sensory neuropathy, scleromalacia perforans, high titer rheumatoid factor, positive visceral angiography, cryoglobulinemia, hypocomplementemia, circulating immune complexes, and histologic necrotizing vasculitis or vascular transmural neutrophilia. Digital lesions or sensory neuropathy alone were not viewed as portending an ominous prognosis by most respondents and would have been treated with nonsteroidal anti-inflammatory drugs, antimalarials, gold salts, or D-penicillamine. Other clinical manifestations considered as reflecting rheumatoid vasculitis (gangrene, mononeuritis multiplex, ulcers) were thought to worsen prognosis and would have been managed more often with corticosteroids, D-penicillamine, cytotoxic agents or plasmapheresis. Rheumatoid vasculitis is viewed as a heterogeneous group of syndromes with varying clinical and histopathologic features,which have different prognostic implications, and therefore should be managed differently. While these dta do not substitute for an extensive recorded series of patients, they provide useful information about community perceptions of an uncommon but difficult clinical problem. They identify the need for additional data to examine the validity of these attitudes.
Gene expression determinants of clinical outcome.

Purpose of review Gene expression profiling of human cancers has produced a large amount of information that could aid physicians in making decisions related to the treatment of their patients. A number of recent studies have identified collections of genes and corresponding expression levels that correlate with the physical appearance and clinical behavior of all common human neoplasms. Recent findings This article will discuss emerging trends of study design and approaches to gene expression signature identification. Recently discovered gene expression signatures that correlate with cellular morphology, resistance to chemotherapy, and overall clinical course of disease are discussed. Summary The prospective evaluation of the predictive value of a number of gene signatures is now appropriate. Newly discovered gene expression signatures that correlate with disease clinical course should be independently evaluated. The timely reporting of both positive and negative results from such validation attempts will be crucial to the advancement of molecular pathology.
Nilpotent and solvable radicals in locally finite congruence modular varieties

The Loewy rank of a modular latticeL of finite height is defined as the leastn for which there exista0=0<at, < ... <ar=1 inL such that each interval I[ai, ai+1] is a complemented lattice. In this paper, a generalized notion of Loewy rank is applied to obtain new results in the commutator theory of locally finite congruence modular varieties. LetV be a finitely generated congruence modular variety. We prove that every algebra inV has a largest nilpotent congruence and a largest solvable congruence. Moreover, there exist first order formulas which define these special congruences in every algebra ofV.
Evidence for a local crustal root beneath the Santa Catalina metamorphic core complex, Arizona

We used data from the Tucson, Arizona, broad-band seismic station to analyze crustal and mantle structure under and adjacent to the Catalina metamorphic core complex. The data can be modeled with a simple two-layer crust having an average Moho depth of ∼30 km and seismic velocities consistent with a felsic composition. The lower crust thickens under the Catalina Mountains, depressing the Moho by ∼4.2 km. The crustal root can isostatically compensate the average topography of the Catalina Mountains, indicating that the depth of isostatic compensation is at or below the Moho and that the Catatina Mountains act as a coherent block bounded by high-angle normal faults. The presence of the crustal root is not consistent with models that predict upward bowing of the Moho under the Catalina metamorphic core complex. The presence of the root cannot rule out models of lower crustal flow during the formation of the core complex. However, the presence of a root favors a model of metamorphic core complex development described by crustal thickening in shortening episodes (crustal-welt model) followed by collapse of the crustal welt through extension.
Tensile Properties and Microstructure of SiC Nanoparticle-Reinforced Mg-4Zn Alloy Fabricated by Ultrasonic Cavitation-Based Solidification Processing

Magnesium, the lightest structural metal, is of significance to improve energy efficiency in various applications. Mg-4Zn/1.5 pct SiC nanocomposites were successfully fabricated by ultrasonic cavitation–based dispersion of SiC nanoparticles in Mg-4Zn alloy melt. As compared to the Mg-4Zn magnesium alloy matrix, the tensile properties including tensile strength, yield strength, and ductility of the Mg-4Zn/1.5 pct SiC nanocomposites were improved significantly. In the microstructure of Mg-4Zn/1.5 pct SiC nanocomposites, there are still some SiC microclusters. However, in areas outside the microclusters, the SiC nanoparticles were dispersed very well. Transmission electron microscopy (TEM) study of the interface between the SiC nanoparticles and Mg-4Zn magnesium alloy matrix suggested that SiC nanoparticles bonded well with Mg without forming an intermediate phase.
John Stuart Mill and the model city Charter

Mill, writing more than a generation before our Committee on a Municipal Program reported the Model Charter, advanced the same principles which we now advocate.
Chinese IPO activity, pricing, and market cycles

We examine the activity, pricing, and market cycles of 1,380 Chinese A share IPOs over the period 1991–2005 and find initial underpricing of 238%. The government restrictions on IPO offer price and quota allocation cause pricing structural breaks and attribute more than half of initial underpricing. A multifactor model that includes firm’s characteristics, excess demand for IPO shares, and the government restrictions explains cross-sectional initial returns, after controlling for industrial differences and stock market conditions. In addition, monthly IPO volume and average initial return are highly correlated. A VAR model indicates that initial return leads IPO volume by 6 months.
The Birth of Modern Urban Governance A Comparison of Political Modernization in Boston, Massachusetts, and Bristol, England, 1800-1870

Although there is little dispute that modern urban governance was born in the nineteenth century in Britain and the United States, several questions have been left unanswered by past and current inquiries into the formation of modern urban governing institutions. For example, what specifically in the historical context of the early nineteenth century convinced political leaders that new forms of urban governance were warranted? How did the first efforts at urban political modernization proceed? Finally, did the early nineteenth-century formation and development of urban governing institutions follow similar paths cross-nationally, or did patterns of modernization diverge sharply across nations? In this article, the author attempts to answer these questions about the birth of modern forms of governance in Boston, Massachusetts, and Bristol, England.
Cache behavior of combinator graph reduction

The results of cache-simulation experiments with an abstract machine for reducing combinator graphs are presented. The abstract machine, called TIGRE, exhibits reduction rates that, for similar kinds of combinator graphs on similar kinds of hardware, compare favorably with previously reported techniques. Furthermore, TIGRE maps easily and efficiently onto standard computer architectures, particularly those that allow a restricted form of self-modifying code. This provides some indication that the conventional "stored program" organization of computer systems is not necessarily an inappropriate one for functional programming language implementations.This is not to say, however, that present day computer systems are well equipped to reduce combinator graphs. In particular, the behavior of the cache memory has a significant effect on performance. In order to study and quantify this effect, trace-driven cache simulations of a TIGRE graph reducer running on a reduced instruction-set computer are conducted. The results of these simulations are presented with the following hardware-cache parameters varied: cache size, block size, associativity, memory update policy, and write-allocation policy. To begin with, the cache organization of a commercially available system is used and then the performance sensitivity with respect to variations of each parameter are measured. From the results of the simulation study, a conclusion is made that combinator-graph reduction using TIGRE runs most efficiently when using a cache memory with an allocate-on-write-miss strategy, moderately large block size (preferably with subblock placement), and copy-back memory updates.
Infrared studies of the oxygen-deficient triperovskite YBa2Cu3−xFexO7+y compound

Abstract Infrared (IR) spectra of the Fe-doped high-temperature superconducting material YBa 2 Cu 3− x Fe x O 7+ y are presented. Our experimental results verify that the P 2 (590 cm -1 ) and P 5 (360 cm -1 ) peaks, which are not detectable in high oxygen content samples of YBa 2 Cu 3 O 7−δ , are completely screened by free carriers of two dimensional CuO 2 networks. The correlation between the infrared intensity of P 2 and that of P 5 has been determined, and it indicates that the P 5 peak corresponds to the asymmetrical CuO bond bending mode E u of the two dimensional CuO 2 network. Either the increasing difficulty in removing the oxygen from the Fe-doped sample or the additional oxygen atoms occupying the O 5 site to form Fe-O 5 -Fe and Fe-O 5 -Cu complex centers along the a axis makes the P 1 (630 cm -1 ) peak obscure in IR spectra of the high-temperature quenched samples of YBa 2 Cu 3− x Fe x O 7+ y ( x ⩾0.2). The intensities of two IR spectra absorption peaks related to the Fe-O bonds imply that two Fe atoms may preferentially form a pair with a bridge of one oxygen atom on the a axis. Based on the IR spectra of YBa 2 Cu 3− x Fe x O 7+ y , a structural model of the intermediate layer (Cu 1− x Fe x O 1+ y ) has been suggested.
Technology and the Family: An Overview From the 1980s to the Present

In 1985 Marriage and Family Review was on the cutting edge of the home computer revolution when it published a thematic issue entitled “Personal Computers and the Family.” Marvin Sussman, editor, b...
Specific heat of some trans-uranium intermetallic compounds — search for heavy fermions

Abstract We measured the low temperature specific heat of single-phase samples of PuRh2, PuGa3, and NpCd11. These materials are candidates for heavy fermion behavior based on their structures and, in the case of PuRh2, on other existing measurements such as magnetic susceptibility. We find rather large γ values for PuGa3 (225 mJ mol−1 K−2) and PuRh2 (145 mJ mol−1 K−2), while that for NpCd11 (10 mJ mol−1 K−2) is low enough to suggest that another channel of behavior (e.g. magnetism) uses up the available f-electron entropy.
Knowledge technologies and business alignment

Achieving lasting, profitable growth is often a matter of maintaining “alignment”. Companies need to ensure that their strategy, organization, processes, culture and systems remain mutually supportive ‐ i.e. “aligned” ‐ rather than in conflict. Information technology can be a powerful tool for helping complex companies stay aligned. Of particular promise is the relatively new set of technologies known as “knowledge technologies” ‐ networks, groupware like Lotus Notes, WWWebware, etc. ‐ that in combination provide a breadth, depth, and immediacy of communication and knowledge sharing not available in any other single medium. Describes a philosophy and an approach for improving business alignment through knowledge technologies.
Online correction of catheter movement using CT in high-dose-rate prostate brachytherapy

Purpose To present a clinical procedure that readjusts catheters to its planned positions based on pretreatment computed tomography (CT) for patients undergoing high-dose-rate (HDR) prostate brachytherapy, and evaluate the magnitude and dosimetric impact of the adjustments.
The Role of Factor XIa (FXIa) Catalytic Domain Exosite Residues in Substrate Catalysis and Inhibition by the Kunitz Protease Inhibitor Domain of Protease Nexin 2

To select residues in coagulation factor XIa (FXIa) potentially important for substrate and inhibitor interactions, we examined the crystal structure of the complex between the catalytic domain of FXIa and the Kunitz protease inhibitor (KPI) domain of a physiologically relevant FXIa inhibitor, protease nexin 2 (PN2). Six FXIa catalytic domain residues (Glu98, Tyr143, Ile151, Arg3704, Lys192, and Tyr5901) were subjected to mutational analysis to investigate the molecular interactions between FXIa and the small synthetic substrate (S-2366), the macromolecular substrate (factor IX (FIX)) and inhibitor PN2KPI. Analysis of all six Ala mutants demonstrated normal Km values for S-2366 hydrolysis, indicating normal substrate binding compared with plasma FXIa; however, all except E98A and K192A had impaired values of kcat for S-2366 hydrolysis. All six Ala mutants displayed deficient kcat values for FIX hydrolysis, and all were inhibited by PN2KPI with normal values of Ki except for K192A, and Y5901A, which displayed increased values of Ki. The integrity of the S1 binding site residue, Asp189, utilizing p-aminobenzamidine, was intact for all FXIa mutants. Thus, whereas all six residues are essential for catalysis of the macromolecular substrate (FIX), only four (Tyr143, Ile151, Arg3704, and Tyr5901) are important for S-2366 hydrolysis; Glu98 and Lys192 are essential for FIX but not S-2366 hydrolysis; and Lys192 and Tyr5901 are required for both inhibitor and macromolecular substrate interactions.
Ectopic B-Raf expression enhances extracellular signal-regulated kinase (ERK) signaling in T cells and prevents antigen-presenting cell-induced anergy

T cells that receive stimulation through the T cell receptor (TCR) in the absence of costimulation become anergic and are refractory to subsequent costimulation. This unresponsiveness is associated with the constitutive activation of the small G protein, Rap1, and the lack of Ras-dependent activation of ERK. Recent studies suggest that Rap1 can activate the MAP kinase kinase kinase B-Raf that is either endogenously or ectopically expressed. Peripheral T cells generally do not express B-Raf; therefore, to test the hypothesis that ectopic expression of B-Raf could permit Rap1 to activate ERK signaling, we generated transgenic mice expressing B-Raf within peripheral T cells. This converted Rap1 into an activator of ERK, to enhance ERK activation and proliferation following TCR engagement in the absence of costimulation. When T cells were incubated with engineered APCs presenting antigen on I-Ek and expressing low levels of B7, they became anergic, displayed constitutive activation of Rap1, and were deficient in Ras and ERK activation. However, when incubated with the same APCs, T cells expressing the B-Raf transgene proliferated upon restimulation and displayed elevated ERK activation. Thus B-Raf expression and enhanced ERK activation is sufficient to prevent anergy in a model of APC-induced T cell anergy. However, studies using anti-TCR antibody-induced anergy showed that the ability of ERKs to reverse T cell anergy is dependent on the anergic model utilized.
Can the natural diversity of quorum-sensing advance synthetic biology?

Quorum-sensing networks enable bacteria to sense and respond to chemical signals produced by neighboring bacteria. They are widespread: over one hundred morphologically and genetically distinct species of eubacteria are known to use quorum sensing to control gene expression. This diversity suggests the potential to use natural protein variants to engineer parallel, input-specific, cell-cell communication pathways. However, only three distinct signaling pathways, Lux, Las, and Rhl, have been adapted for and broadly used in engineered systems. The paucity of unique quorum-sensing systems and their propensity for crosstalk limits the usefulness of our current quorum-sensing toolkit. This review discusses the need for more signaling pathways, roadblocks to using multiple pathways in parallel, and strategies for expanding the quorum-sensing toolbox for synthetic biology.
Primary Hemangio-Endothelioma of the Heart: Report of a Case

Among the sixty-odd cases of primary malignant tumors of the heart and pericardium reported in the literature, four lymphangio-endotheliomas of the heart (1–4) and one angiosarcoma of the pericardium (5) are listed. Three of the four cases of lymphangio-endothelioma caused heart-block. The angiosarcoma of the pericardium gave the symptoms of pericarditis. Only one case of hemangio-endothelioma of the heart was found in the literature. This case was reported by Penneman (6) in 1908. The tumor, 1.5 × 2.5 × 3.0 cm., was an incidental, unsuspected autopsy finding in a seventy-year-old woman whose heart was otherwise normal. The case here presented is, to our knowledge, only the second case of hemangio-endothelioma of the heart to be recorded. Case Report A fortv-five-year-old white woman was admitted to the Western Pennsylvania Hospital complaining of spasms in the left arm. She had had rheumatic fever at the age of twenty-five, and for the past two years had been treated at the cardiac clinic for rheumatic heart disease. During this time fibrillation was continuous except for a period of twenty-seven days, four months previous to admission, when the rhythm was normal as a result of quinidine therapy. Several days prior to admission hemiplegia developed on the left side.
How SOX affects investing through credit rating agencies

The Sarbanes-Oxley Act (SOX) has a long reach. Is your firm issuing debt or other securities? Or are you concerned about the cost of capital? Are you responsible for structuring financial transactions or for making investments? Then you may be surprised to learn that SOX Section 702(b) can affect all these activities and more. It regulates the hugely important credit rating agencies. © 2004 Wiley Periodicals, Inc.
Psychological Functioning in Children and Adolescents Undergoing Radiofrequency Catheter Ablation

This study examined 38 patients (age 6–18 years) with recurrent cardiac arrhythmias who underwent radiofrequency catheter ablation of ectopic myocardial foci. Psychological functioning was assessed by the Pediatric Symptom Checklist, Short Mood and Feeling Questionnaire, Revised Children's Manifest Anxiety Scale, and Arrhythmia Anxiety Queries prior to ablation and at 3-month follow-up. The patients resembled a normal population without elevations in anxiety or depression. After ablation, the patients showed reductions in the “fear of their heart problem” and increases in “the things that they enjoy.” The patients who underwent a curative ablation had better functioning than those who did not show improvement. Children appear to have the opportunity for an improved quality of life after ablation.
Contextual Classification of Multispectral Remote Sensing Data Using a Multiprocessor System

A statistical model of spatial context is described and procedures for classifying remote sensing data using a context classifier are outlined. Experimental results are presented. Because the computational requirements of the context classifier are very large, its implementation on multiprocessor systems is investigated. Some of the special considerations necessary for such implementations are described, with particular reference to implementation on an array of Control Data Corporation Flexible Processors.
OLDER PERSONS' TV VIEWING PATTERNS AND MOTIVATIONS:

Television viewing motivations and viewing patterns were examined for a sample of 340 aging and aged persons. Correlational relations between viewing motivations and viewing patterns were evident. Viewing motivations were found to be intercorrelated and canonical analysis located associations among viewing motivations and patterns. Companionship, habit, relaxation, arousal, escape, pass time, and product advertising motivations were interrelated and associated with increased television affinity, viewing levels, and game show and daytime serial watching. Information and entertainment motivations were interrelated and associated with news, documentary-magazine, and talk-interview program viewing. Multiple regression analysis determined that the salience of habit, pass time, and entertainment viewing motivations contributed to increased viewing levels; the salience of habit, companionship, product advertising, and entertainment viewing motivations contributed to increased television affinity. Implications of...
In vivo measurement of regional brain and tumor pH using [14C] dimethyloxazolidinedione and quantitative autoradiography

Summary: Using [14C]dimethyloxazolidinedione ([14C]-DMO) and quantitative autoradiography, we estimated tissue pH (pHt) and intracellular pH (pHi) in nine regions of the normal rat brain and in intracerebrally implanted RG-2 gliomas. Calculations of regional pHt, based on equilibrium tissue and arterial plasma [14C]DMO concentration, ranged from 6.83 to 6.94; pHi, calculated assuming an extracellular water volume of 0.15 ml/g for gray matter and 0.11 ml/g for white matter, ranged from 6.61 to 6.78. No consistent difference was found in pHt or pHi between white and gray matter regions. Tumor tissue water content was determined by drying to constant weight, and extracellular space water volume (Ve) was estimated with [l4C]sucrose in nephrectomized rats using quantitative autoradiography. Tumor pHt ranged from 7.08 to 7.18. For Ve = 0.17 (measured), pHi was 6.94-7.06; for Ve = 0.30 (assumed), the corresponding range for pHi was 6.63-6.90. Thus, the RG-2 glioma is not more ''acidic” than adjacent brain tissue and its “alkaline” pHt probably reflects a large extracellular water content and plasma-like extracellular pH.
Stability Constants for Complex Formation Between α-Cyclodextrin and Some Amines

Complex formation of alpha-cyclodextrin with 15 amines (including seven 4-substituted anilines) was studied by the potentiometric method, supplemented by direct UV spectrophotometry and a competitive indicator spectrophotometric method. The data were analyzed in terms of 1:1 and 1:2 complexes (amine-cyclodextrin ratios) and the stability constants K11a, K12a, K11b, and K12b were evaluated; the subscripts indicate the stoichiometry and conjugate acid-base form. For all amines K11b was greater than K11a and K12a was 0. On the basis of the relationship of complex stability to amine structure, it was concluded that the primary binding site in anilines is the 4-substituent.
Effects of hypothermia on cortico-cortical modulation of evoked activity in cat visual cortex.

Abstract The functional significance of the reciprocal connections between areas 17 and 18 of the cat visual cortex was investigated by the reversible suppression of the activity of cells whose axons project to neighboring cortex. This was accomplished by selectively cooling either area 17 or area 18 in a controlled manner while maintaining the adjacent cortex at normal temperature. Moderate cooling of area 17 in the range from 25° to 28°C produced an enhancement in the surface potentials elicited from the dorsal lateral geniculate nucleus and in the total unit discharge in the adjacent area 18. By cooling area 18 a corresponding effect was produced in the adjacent area 17. A mechanism of inhibitory cortico-cortical loop fibers running between areas 17 and 18 is hypothesized to explain these effects.
Inhibition of the ovarian augmentation reaction by a chemical antiestrogen.

Inhibition by antiestradiol serum of ovarian weight gain and follicular growth in hypophysectomized immature rats given FSH and hCG suggested that gonadotrophin induced endogenous estrogen secretion plays a role in the ovarian augmentation reaction. We have studied the effects of a chemical estrogen antagonist, cis-clomiphene, on ovarian weight response to gonadotrophins in hypophysectomized immature female rats. We found that this antiestrogen inhibits the ovarian response to FSH and hCG. To our knowledge, this is the first demonstration of a direct effect of a chemical antiestrogen on the ovary, a result consistent with a role for intraovarian estrogen in follicular growth. (Endocrinology 96: 1119, 1975)
Adopting, Adapting, and Opting Out: State Response to Federal Voting System Guidelines

This article examines the state response to voluntary federal certification of electronic voluntary voting system guidelines (VVSGs) and current intergovernmental issues surrounding electronic voting systems across the country. Federal certification is not widespread, and most states have adapted modified methods of assuring system integrity or have opted out altogether. States that participate in VVSG have greater technological sophistication, higher levels of election administration professionalism, and are more likely to adopt touchscreen voting machines. Unlike other election administration reforms, VVSG does not appear to be linked to partisan political factors. Our findings have implications for understanding the limits of voluntary federal programs and the importance of technological capacity and professional human resources in American election administration.
Prevention, Community Services and Proposition 36

The Prevention Panel of the Therapeutic Jurisprudence conference presented several examples of community services and prevention policies that should be brought into the mix of services and supports for Prop 36 and for other court diversion programs. This article summarizes those presentations and suggests how they might be put to work as effective alternatives to incarceration.
Automated analysis of courtship suppression learning and memory in Drosophila melanogaster

Study of the fruit fly, Drosophila melanogaster, has yielded important insights into the underlying molecular mechanisms of learning and memory. Courtship conditioning is a well-established behavioral assay used to study Drosophila learning and memory. Here, we describe the development of software to analyze courtship suppression assay data that correctly identifies normal or abnormal learning and memory traits of individual flies. Development of this automated analysis software will significantly enhance our ability to use this assay in large-scale genetic screens and disease modeling. The software increases the consistency, objectivity, and types of data generated.
Highly variable reproductive isolation among pairs of Catostomus species

Hybridization between diverged taxa tests the strength of reproductive isolation and can therefore reveal mechanisms of reproductive isolation. However, it remains unclear how consistent reproductive isolation is across species' ranges and to what extent reproductive isolation might remain polymorphic as species diverge. To address these questions, we compared outcomes of hybridization across species pairs of Catostomus fishes in three rivers in the Upper Colorado River basin, where an introduced species, C. commersoni, hybridizes with at least two native species, C. discobolus and C. latipinnis. We observed substantial heterogeneity in outcomes of hybridization, both between species pairs and across geographically separate rivers within each species pair. We also observed hybridization of additional related species with our focal species, suggesting that reproductive isolation in this group involves interactions of multiple evolutionary and ecological factors. These findings suggest that a better understanding of the determinants of variation in reproductive isolation is needed and that studies of reproductive isolation in hybrids should consider how the dynamics and mechanisms of reproductive isolation vary over ecological space and over evolutionary time. Our results also have implications for the conservation and management of native catostomids in the Colorado River basin. Heterogeneity in outcomes of hybridization suggests that the threat posed by hybridization and genetic introgression to the persistence of native species probably varies with extent of reproductive isolation, both across rivers and across species pairs.
Abstract LB-141: Expression and localization of Id3 in human prostate cancer

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Purpose: The inhibitor of differentiation (Id) proteins are dominant negative basic helix-loop-helix family of transcription factors that lack the DNA-binding basic domain but have intact HLH domain. The four members of the Id protein family (Id1-Id4) are known to play a critical role in the coordinated regulation of gene expression during cell growth, differentiation and tumorigenesis. Although in vitro studies have demonstrated the role of Id1 in regulating prostate cancer (PCa) cell proliferation, apoptosis and androgen independence, its clinical significance in PCa remains controversial. On the other hand there is lack of evidence on the expression of Id2 and Id3 in PCa progression. Studies have demonstrated that silencing of Id3 is significantly more effective in blocking proliferation of PCa cells as compared to Id1 whereas Id2 silencing has been primarily shown to be involved in apoptotic pathway. Hence in this study we re-evaluated the role of Id1 in PCa and extended our study to show that Id3 protein expression has better clinical relevance compared to Id1 and Id2 in PCa. Experimental design: The expression of Id-1, -2 and -3 was determined by real time and Western blotting along with their sub-cellular localization by ICC in PCa cell lines LNCaP, DU145 and PC3. To assess their significance in prostate cancer progression, the protein expression was investigated in clinical prostate tumor samples on high density tissue microarray by IHC. Results: The expression of Id1 and Id3 mRNA was low in LNCaP and DU145 as compared to PC3 whereas the level of Id2 expression was similar between all the PCa cell lines. The protein expression data was consistent with the mRNA levels in the PCa cell lines. All three Id's were primarily cytoplasmic with some nuclear presence. The IHC data showed a significant increase in the expression of Id1 and Id3 in clinical prostate tumor tissue samples compared to normal prostate tissue whereas Id2 showed elevated levels but was not significant as compared to Id1 and Id3. The expression of Id3 protein correlated with the Gleason grading and stage of PCa. Conclusions: This is the first study demonstrating a correlation between increased expression of Id3 and prostate cancer progression. It also reconfirms and establishes the association of Id1with PCa. The results warrant further investigation into isoform specific effects of Id1and Id3 on prostate tumorigenesis. (Research Support: NIH/NCI RO1 [CA128914][1] and NIH/NCRR/RCMI G12RR03062. The first two authors contributed equally to this work. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-141. doi:10.1158/1538-7445.AM2011-LB-141 [1]: /lookup/external-ref?link_type=GEN&access_num=CA128914&atom=%2Fcanres%2F71%2F8_Supplement%2FLB-141.atom