cssi/SciSciGPT-SciSciNet huggingface dataset:
Significance of ER–Src axis in hormonal therapy resistance

The estrogen receptor (ER) is implicated in the progression of breast cancer. Despite positive effects of hormonal therapy, initial or acquired resistance to endocrine therapies frequently occurs. Recent studies suggested ERα-coregulator PELP1 and growth factor receptor ErbB2/HER2 play an essential role in hormonal therapy responsiveness. Src axis couples ERα with HER2 and PELP1, thus representing a new pathway for targeted therapy resistance. To establish the significance of ER–Src axis in PELP1 and HER2 mediated therapy resistance, we have generated model cells that stably express Src-shRNA under conditions of PELP1, HER2 deregulation. Depletion of Src using shRNA substantially reduced E2 mediated activation of Src and MAPK activation in resistant model cells. Pharmacological inhibition of Src using dasatinib, an orally available inhibitor substantially inhibited the growth of therapy resistant MCF7–PELP1, MCF7–HER2, and MCF7–Tam model cells in proliferation assays. In post-menopausal xenograft based studies, treatment with dasatinib significantly inhibited the growth of therapy resistant cells. IHC analysis revealed that the tumors were ERα positive, and dasatinib treated tumors exhibited alterations in Src and MAPK signaling pathways. Combinatorial therapy of tamoxifen with dasatinib showed better therapeutic effect compared to single agent therapy on the growth of therapy resistant PELP1 driven tumors. The results from our study showed that ER–Src axis play an important role in promoting hormonal resistance by proto-oncogenes such as HER2, PELP1, and blocking this axis prevents the development of hormonal independence in vivo. Since PELP1, HER2, and Src kinase are commonly deregulated in breast cancers, combination therapies using both endocrine agents and dasatinib may have better therapeutic effect by delaying the development of hormonal resistance.
Ultratrace Determination of Selenium by Hydride Generation–Inductively Coupled Plasma Mass Spectrometry Operated Under Nonrobust Plasma Conditions

Abstract A hydride generation–inductively coupled plasma mass spectrometer (HG‐ICPMS) operated at low RF power (720 W) was demonstrated to be suitable for ultra trace determination of Se, which is an element with high ionization potential (IP). 78Se analysis free from 38Ar40Ar spectral interference was achieved by operating the plasma under a so‐called warm plasma condition (as opposed to traditionally defined hot and cool plasmas). In this warm plasma, there is a sufficient population of energetic Ar+ to ensure ionization of Se, while the number of 38Ar40Ar ions is at the minimum, due to the dimer's bimodal profile. A detection limit of 1 ng/L was achieved for 78Se. Background spectra of warm and hot plasmas were compared. Two types of HG gas–liquid separators were compared. The technique was applied to measure trace amounts of Se in atmospheric samples; namely, cloud water and aerosol particulate. Good agreement was found between HG warm plasma ICPMS and pneumatic micronebulization hot plasma ICPMS for ...
A stochastic compartmental model of bone cells

Cellular dynamics play an important role in bone remodelling. The mesenchymal cells, osteoclasts, osteoblasts and osteocytes are the four types of bone cells, which mediate bone remodelling involving bone formation and resorption throughout the human life-span. A stochastic compartmental model of bone cells is formulated in the present analysis assuming these four types of cells to be in four distinct compartments. The cumulant generating function is first derived using the transition parameters for intercompartmental diffusion. Equations for the mean, variance and covariance for the number density of these cells are then derived from the partial differential equation for the cumulant generating function. The simulation results are consistent with previous experimental observations.
Identification, Quantitation, and Cellular Localization of PDE1 Calmodulin-Stimulated Cyclic Nucleotide Phosphodiesterases

The calmodulin-stimulated cyclic nucleotide phosphodiesterases (PDE1s) constitute a large gene family and are found in a wide variety of tissues and cells. Because of the functional diversity of PDE1 genes and the observation that these isozymes often make up a major component of the total cyclic nucleotide hydrolytic activity in certain cell types, PDE1s are of growing interest as targets for therapeutic intervention. Here we describe a series of methodologies to identify, quantitate, and determine the cellular expression of PDE1 isozymes. We describe first the resolution of different PDEs using high-performance anion-exchange chromatography and then a Western blotting methodology for identifying or authenticating PDE1 activities. Next we present an immunoprecipitation method that can be used for quantitating specific PDE1 isoforms and describe the use of RNase protection analysis for further identification of PDE1 subtypes. Finally, we provide a simple, immunocytochemical method for determining the cellular expression of PDE1 isozymes. Combined, the above methodologies should allow an investigator to identify, quantitate, and determine the cellular localization of PDE1 isozymes in any tissue with little ambiguity.
Are We Covering Our Own Backyards?: An Analysis of Local Research Guides Created by Academic Business Librarians.

This study examines local research guides created by academic business librarians to assist patrons with researching the communities (towns, cities, and regions) where their schools are located. A key finding is that only 33% of the libraries surveyed provide guides to local research, while 80% provide guides to international research.
Developmental expression of Ki-67 antigen and proliferating cell nuclear antigen in macaque placentas

Placental growth is largely determined by the proliferation of cytotrophoblast cells. However, the distribution of cytotrophoblast cells engaged in the cell cycle during placental development is poorly understood. Recently, antibodies have been developed that identify two proteins directly involved with DNA synthesis: Ki-67 protein and proliferating cell nuclear antigen (PCNA). Immunolocalization of Ki-67 and PCNA provides a measure of the proliferating cells in tissues. We examined, in macaque placentas, the spatiotemporal pattern of expression of these proteins during gestation. Tissues from 24 macaque placentas collected from 22–153 days of pregnancy were prepared for paraffin sections. Standard immunoperoxidase techniques were used to identify Ki-67 and PCNA. The proteins generally co-localized, although PCNA was usually represented in more cells than Ki-67. Early in gestation the cell columns contained many labeled cells. The cytotrophoblastic shell was occupied by numerous cells with PCNA positive nuclei, but few were reactive for Ki-67. By 45 days of pregnancy the immunolabeled cells in the cell columns were concentrated in the proximal regions, adjacent to the anchoring villus tips. The number of positive cells descreased by 100 days when the cell columns were diminished, leaving the anchoring villus tips buried in the shell. Labeled cells were rarely present in the shell at late pregnancy. The single layer of cytotrophoblast cells in the chorionic plate contained numerous reactive cells throughout early and mid-gestation. After approximately 100 days the cytotrophoblast layer of the chorionic plate was stratified over large areas. Soon thereafter few cells of the chorionic plate were labeled. The chorionic villi contained reactive cytotrophoblastic cells throughout gestation. Extravillous cytotrophoblast cells invading spiral arteries were sometimes labeled for PCNA but not Ki-67. We conclude that compartments of the placenta are distinguished by specific patterns of cytotrophoblast cell proliferation. Moreover, these patterns correspond to macroscopic growth parameters of the placenta. Evidence suggests that the macaque placenta slows its rate of diametrical growth at approximately 100 days of gestation. It is at about this time that the cell columns are absorbed into the trophoblastic shell and this pool of proliferating cells is diminished. The growth in diameter of the chorionic plate matches that of the shell. In this compartment also the architecture changes at about 100 days as the cytotrophoblast layer stratifies. This stratification may result from continued proliferation of cytotrophoblast cells when the diametrical rate of growth is decreasing. Soon thereafter, proliferation decreases in this compartment also. By contrast, labeled cells were found in chorionic villi throughout gestation. Continued villous growth and branching probably accounts for most of the increases in placental thickness and weight that occurs during late gestation. © 1994 Wiley-Liss, Inc.
Elicitation by Critiquing: An Exploratory Study

Knowledge elicitation methods uncover information about how a practitioner works in a field. However, these methods have the challenges of grounding in context, accessibility to experts and tasks, ...
Kinetics of Reductive N−O Bond Fragmentation: The Role of a Conical Intersection

N-alkoxyheterocycles can act as powerful one-electron acceptors in photochemical electron-transfer reactions. One-electron reduction of these species results in formation of a radical that undergoes N-O bond fragmentation to form an alkoxy radical and a neutral heterocycle. The kinetics of this N-O bond fragmentation reaction have been determined for a series of radicals with varying substituents and extents of delocalization. Rate constants varying over 7 orders of magnitude are obtained. A reaction potential energy surface is described that involves avoidance of a conical intersection. A molecular basis for the variation of the reaction rate constant with radical structure is given in terms of the relationship between the energies of the important molecular orbitals and the reaction potential energy surface. Ab initio and density functional electronic structure calculations provide support for the proposed reaction energy surface.
Beyond the least-cost path: evaluating corridor redundancy using a graph-theoretic approach

The impact of the landscape matrix on patterns of animal movement and population dynamics has been widely recognized by ecologists. However, few tools are available to model the matrix’s influence on the length, relative quality, and redundancy of dispersal routes connecting habitat patches. Many GIS software packages can use land use/land cover maps to identify the route of least resistance between two points—the least-cost path. The limitation of this type of analysis is that only a single path is identified, even though alternative paths with comparable costs might exist. In this paper, we implemented two graph theory methods that extend the least-cost path approach: the Conditional Minimum Transit Cost (CMTC) tool and the Multiple Shortest Paths (MSPs) tool. Both methods enable the visualization of multiple dispersal routes that, together, are assumed to form a corridor. We show that corridors containing alternative dispersal routes emerge when favorable habitat is randomly distributed in space. As clusters of favorable habitat start forming, corridors become less redundant and dispersal bottlenecks become visible. Our approach is illustrated using data from a real landscape in the Brazilian Atlantic forest. We explored the effect of small, localized disturbance on dispersal routes linking conservation units. Simulated habitat destruction caused the appearance of alternative dispersal routes, or caused existing corridors to become narrower. These changes were observed even in the absence of significant differences in the length or cost of least-cost paths. Last, we discuss applications to animal movement studies and conservation initiatives.
Intermediate structure in the giant E1 resonance in the 19F(p, γ0)20Ne reaction

Abstract The striking intermediate structure observed in the giant E1 resonance of 20Ne has been studied with the polarized and unpolarized 19F(p, γ0)20Ne reaction. A heuristic model of four intermediate doorway resonances is found to fit the data.
Insular Biogeographic Theory and Diffusion Models in Population Dynamics

Abstract We examine a class of mathematical models describing the effects of habitat size and geometry on community structure. We deduce spatial effects at the community level from mechanistic models for the population dynamics and dispersal of individual populations together with some minimal hypotheses about the distribution of growth and dispersal rates among those populations. We use the models to deduce species-area curves, and in that sense they provide an alternative to the dynamic equilibrium theory of island biogeography introduced by MacArthur and Wilson. Since the models can explicitly incorporate various hypotheses about population dynamics and the nature and strength of interactions between species they permit a detailed analysis of how these hypotheses should affect community structure. We illustrate that point by contrasting the implications of different hypotheses in the context of refuge design.
Effects of different substrates on glucose uptake and hexokinase activity in Euglena gracilis.

SYNOPSIS. Hexokinase levels and glucose uptake rates were measured in cells of Euglena gracilis adapted for growth on glucose, acetate, and ethanol. Glucose-grown cells had 3 times the hexokinase levels found in acetate- and ethanol-grown cells. However, glucose- and ethanol-grown cells had the same rates of glucose uptake, while acetate-grown cells accumulated only 1/8 as much glucose in the same interval.
Toward consistent use of reporting scales in imaging studies.

This editorial refers to the article “Potential effect of different radiologist reporting methods on studies showing benefit of CAD” by Horsch et al in the present issue of Academic Radiology (1). There are several communities or “cultures” that will find common ground in this article. One community includes the public and private funding sponsors and developers of new technologies for medical imaging—in particular, the technology of computer algorithms that assist radiologists in their decision making. Another community therefore is that of the radiologists themselves who will use these technologies. Then there is the community developing study designs and statistical assessment methodologies for evaluating the new technologies. Downstream we encounter the community of public policy makers who approve and clear these technologies for entrance to the marketplace for their specified task and the third-party payers who determine when a combination of a technology and a diagnostic task meet their criteria for reimbursement. The pace of advance of the technology community is fairly obvious, particularly at the many professional society meetings throughout the year. A prime example of an advance in the radiology profession— especially in the particular setting of the present article— has been the evolution of consensus development by the Breast Imaging Reporting and Data Systems (BIRADS) committee of the American College of Radiology (2).
Physiological de Novo Thyroid Hormone Formation in Primary Culture of Porcine Thyroid Follicles: Adenosine 3′,5′-Monophosphate Alone Is Sufficient for Thyroid Hormone Formation*

We describe a method of culturing intact porcine thyroid follicles for physiological de novo thyroid hormone formation; the roles of cAMP and protein kinase-C in thyroid hormone formation were also studied. Thyroid follicles were obtained by digesting minced porcine thyroid tissue with 0.04% collagenase and cultured in Coon's Modified Ham's F-12 medium supplemented with 0.5% calf serum, 0.5 mU/ml TSH, other standard hormones, and 3 antibiotics (6H medium). On the fourth day of culture, 6000-8000 follicles/well were plated in 12-well culture dishes. On the sixth day, thyroid hormone formation was carried out by incubating thyroid follicles with 0.5 microM KI in the presence of 6H medium for 2 days in a 5% CO2-95% air incubator at 37 C. To examine the effects of cAMP and protein kinase-C on de novo thyroid hormone formation, follicles were incubated with KI in the presence of 1-2.5 mM (Bu)2cAMP, 10 microM forskolin, 2 microM prostaglandin E2 (PGE2), or 0.5-1 microM 12-O-tetradecanoylphorbol-13-acetate in TSH-free medium for 2 days. The amount of newly formed thyroid hormone was measured by RIA of T3 content in the Pronase digest of thyroid follicular cells. Thyroid follicles cultured in 6H medium had normal polarity of the membrane, determined by electron microscope, and thyroid cAMP was responsive to the alteration of TSH. In this culture system cAMP alone was sufficient to form thyroid hormone. 12-O-Tetradecanoylphorbol-13-acetate, a protein kinase-C stimulator, disrupted thyroid follicles and inhibited cAMP-mediated thyroid hormone formation. The integrity of follicular structure was also required for thyroid hormone formation in this culture system. This study introduces perhaps the most physiological culture system for de novo thyroid hormone formation. Our data provide direct evidence that thyroid hormone formation is linked to cAMP and that the protein kinase-C system acts as an inhibitor of thyroid hormone formation.
Parallel solution of symmetric positive definite systems with hyperbolic rotations

Abstract An algorithm based on hyperbolic rotations is presented for the solution of linear systems of equations Ax = b, with symmetric positive definite coefficient matrix A. Forward elimination and backsubstitution are replaced by matrix-vector multiplications, rendering the method amenable to implementation on a variety of parallel and vector machines. This method can be simplified and formulated without square roots if A is also Toeplitz; a systolic (VLSI) architecture implementing the resulting recurrence equations is more efficient than previously proposed pipelined Toeplitz system solvers. The hardware count becomes independent of the matrix size if its inverse is banded.
Faraday Loss for L-Band Radar and Communications Systems

The mechanism of Faraday rotation as it affects radar and communication propagation has been extensively treated (1, 7). The purpose of this paper is to point out the magnitude of the effect and its possible consequences which have not been appreciated. Contrary to what many believe, the two-way Faraday rotation angle and loss can be large at L-band for ground-based, linearly polarized radar systems observing targets above the ionosphere. Similarly, the one-way Faraday rotation and loss for linearly polarized, ground-to-space pace communication links at comparable frequencies can be large. The magnitude of the rotation loss depends on the location of the radar or communication station in latitude and longitude, the condition of the ionosphere, and the elevation and azimuth angles of the target. For example, based on the total electron content in 1970 (a peak sunspot activity year) at L-band, a two-way Faraday rotation greater than 50°a loss greater than 3.8 dB is calculated to occur at 60° N, 70° W, 75 percent of the time between the hours of 10 A.M. and 4 P.M. for nine months, and 22 percent of the total time for the entire year, when looking toward the south magnetic pole at low elevation angles. For the same year this rotation and loss at 15°N, 150° is calculated to occur 48 percent of the total time when looking south at low elevation angles.
Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene

Introduction of a normal retinoblastoma gene (RB) into retinoblastoma cells was previously shown to suppress several aspects of their neoplastic phenotype, including tumorigenicity in nude mice, thereby directly demonstrating a cancer suppression function of RB. To explore the possibility of a similar activity in a common adult tumor, RB expression was examined in three human prostate carcinoma cell lines. One of these, DU145, contained an abnormally small protein translated from an RB messenger RNA transcript that lacked 105 nucleotides encoded by exon 21. To assess the functional consequences of this mutation, normal RB expression was restored in DU145 cells by retrovirus-mediated gene transfer. Cells that maintained stable exogenous RB expression lost their ability to form tumors in nude mice, although their growth rate in culture was apparently unaltered. These results suggest that RB inactivation can play a significant role in the genesis of a common adult neoplasm and that restoration of normal RB-encoded protein in tumors could have clinical utility.
The melanopsin system: Phototransduction, projections, functions, and clinical implications

The melanopsin system consists of retinal ganglion cells containing the photopigment melanospin, which are directly activated by light in the absence of inputs from the photoreceptors. These intrinsically photosensitive retinal ganglion cells (ipRGCs) detect environmental brightness; combine their direct, melanospin-triggered photoresponses with signals derived from rods and cones; and project to several targets in the diencephalon and midbrain. Via these projections, the melanospin system mediates several non-imaging-forming visual functions, including light entrainment of circadian rhythms and pupillary responses to light. The discovery of the melanopsin system explained the preservation of normal circadian rhythms, relative preservation of pupillary reflexes, and excessive light sensitivity in patients with visual loss due to disorders affecting the photoreceptors. The melanopsin-containing ipRGCs are relatively spared in inherited mitochondrial optic neuropathies, may be selectively affected in glaucoma, and may trigger photophobia in patients with migraine. Polymorphisms in the melanospin (opsin 4, Opn4) gene are associated with seasonal affective disorder. The functional organization of the melanopsin system and its implications in disease have been recently reviewed.1,–,7 ### Intrinsically photosensitive retinal ganglion cells. Melanopsin (also called opsin 4, Opn4) is a photopigment that was first identified in frog skin and was thereafter detected in a small subpopulation of retinal ganglion cells in vertebrates.8 The ipRGCs respond to light stimulation with depolarization in the absence of any synaptic input from rods and cones; hence their designation as intrinsically photosensitive.1,9 The ipRGCs combine their direct, melanospin-triggered photoresponses with signals derived from rods and cones and project to several targets in the diencephalon and midbrain involved in circadian rhythms and pupil responses to light (figure) The ipRGCs constitute a small percentage of ganglion cells; in each human eye, up to 3,000 out of ∼1.5 million retinal ganglion cells stain positively for melanopsin10; these cells are more concentrated …
Observations concerning the natural history of subclinical hyperthyroidism.

Objective: To examine the natural history of a subnormal serum thyroid-stimulating hormone (TSH) concentration with normal concentrations of both serum free thyroxine (FT4) and free triiodothyronine (FT3) (subclinical hyperthyroidism). Patients, Design, and Measurements: A retrospective analysis was undertaken and yielded 16 ambulatory patients who had presented with subclinical hyperthyroidism and were longitudinally followed with measurements of serum TSH and both FT4 and FT3 for a cumulative follow-up of 11 to 36 months. Seven of the patients had subclinical Graves' hyperthyroidism as judged from the presence of thyroid-stimulating immunoglobulins (TSI) in serum, and 9 had multinodular goiter confirmed with ultrasound and no TSI. Results: In the 7 patients with TSI, serum TSH reverted to normal in 5 patients, with disappearance or decrease of TSI in 4, within 3 to 19 months. In 1 patient, subnormal serum TSH accompanied by both normal FT4 and FT3 has persisted for 15 months, and in a second patient ser...
Surgical versus nonsurgical treatment of femur fractures in people with spinal cord injury: an administrative analysis of risks.

Abstract Objective To assess the risks associated with surgical and nonsurgical care of femur fractures in people with spinal cord injury (SCI). Design Retrospective cohort study; an analysis of Veterans Affairs (VA) data from the National Patient Care Database. Setting Administrative data from database. Participants The cohort was identified by searching the administrative data from fiscal years 2001 to 2006 for veterans with a femur fracture diagnosis using the International Classification of Diseases, 9th Revision, Clinical Modification codes. This group was subdivided into those with (n=396) and without (n=13,350) SCI and those treated with and without surgical intervention. Interventions Not applicable. Main Outcome Measures Rates of mortality and adverse events. Results The SCI group was younger with more distal fractures than the non-SCI group. In the non-SCI population, 78% of patients had associated surgical codes compared with 37% in the SCI population. There was higher mortality in the non-SCI group treated nonoperatively. In the SCI population, there was no difference in mortality between patients treated nonoperatively and operatively. Overall adverse events were similar between groups except for pressure sores in the SCI population, of which the nonoperative group had 20% and the operative had 7%. Rates of surgical interventions for those with SCI varied greatly among VA institutions. Conclusions We found lower rates of surgical intervention in the SCI population. Those with SCI who had surgery did not have increased mortality or adverse events. Surgical treatment minimizes the risks of immobilization and should be considered in appropriate SCI patients.
Nested subset structure of larval mycophagous fly assemblages : nestedness in a non-island system

Nested subset structure has been studied in archipelagoes and fragmented habitats, and has been attributed to differential colonization and extinction rates among species and nested environmental tolerances. In this experiment, we tested for nestedness in assemblages of mycophagous fly larvae. Twenty mushrooms in each of three size classes (4.8-6.0 g, 10-15 g, 21-32 g) were placed on moist potting soil in experimental cups. The cups were placed in oak and pine forests in Greenville, S.C., USA for 5 days, where they were available to ovipositing flies. Upon collection, the mushrooms were incubated in the laboratory for 3 weeks and all emerging flies were sorted by species, counted, and weighed. A random placement analysis was conducted to determine whether the species richness pattern was a sampling artifact of the species abundance distributions. The actual species richness pattern did not conform to the random placement model; most mushrooms contained significantly fewer species than predicted by random sampling. The communities were strongly nested as measured by two different indices, and the nestedness pattern was related to mushroom size. Small mushrooms usually produced no flies or a single species, Dohrniphora sp. (Phoridae). Medium and large mushrooms typically produced more species-rich communities that usually contained the phorid and Drosophila putrida, D. tripunctata, and Leucophenga varia. This core guild was nested within a more diverse assemblage that included D. falleni, Mycodrosophila dimidiata, a muscid, and two Leptocera sp. (sphaeroceridae). These patterns are tentatively explained in the context of nested desiccation tolerances, mediated by differences in mushroom size.
Linking Heme Activation to Conformation Change in Hemoglobin Via Chain Selective Time-resolved Resonance Raman Spectroscopy on Mesoheme Hybrids

Time-resolved Resonance Raman spectra are reported for Hb tetramers, in which the α and β chains are selectively substituted with mesoheme. Hb function is unaffected by the substitution, but the Soret absorbtion band shift in meso- relative to proto-heme permits chain-selective excitation of heme RR spectrum. The evolution of these spectra following HbCO photolysis show that geminate recombination rates and yields are the same for the two chains, consistent with recent results with 15N-heme isotopomer hybrids. The spectra also reveal systematic shifts in the deoxy-heme ν4 and νFe-His RR bands, which are anti-correlated. These shifts are resolved for the successive intermediates in the protein structure, as previously determined from time-resolved UVRR spectra. Both chains show Fe-His bond compression in the immediate photoproduct, which relaxes during the formation of the first intermediate, Rdeoxy (0.07 μs), in which the proximal F-helix is proposed to move away from the heme. Subsequently, the Fe-His bond weakens, more so for the α than the β chains. The weakening is gradual for the β chains, but abrupt for the α chains, coinciding with completion of the R-T quaternary transition, at 20 μs. Since the transition from fast- to slow-rebinding Hb also occurs at 20 μs, the drop in the α chain νFe-His supports the localization of ligation restraint to tension in the Fe-His bond, at least in the α-chains. The mechanism is more complex in the β chains.
The role of death receptor ligands in shaping tumor microenvironment.

Death receptor ligands (FasL, TRAIL) activate apoptosis in cells expressing the cognate receptors. Evidence suggests that these ligands also deliver pro-inflammatory signals. In the tumor microenvironment, “Fas counterattack” mounted by tumors against immune cells is mediated by tumor-associated FasL. But death ligands crosslinking their receptors also induce inhibition of apoptosis and activation of the transcription factor, NFκB, with a subsequent burst of pro-inflammatory cytokine production and tumor growth promotion. NFκB, a key link between inflammation and cancer, regulates dual activities of death ligands, depending on molecular signals in the tumor microenvironment. This paper focuses on death ligands as an example of the extensive repertoire of strategies devised by tumors for escape from immune control.
Colloid Cysts of the Third Ventricle

In this paper 33 cases of colloid cyst of the 3rd ventricle are presented. The initial symptoms as well as the clinical syndromes are quite variable, but usually consist of a combination of signs of increased intracranial pressure and an organic dementia, progressive or paroxysmal. Computed tomography is an invaluable diagnostic tool and it seems that, since it has become widely used in the evaluation of patients with headaches or dementia, colloid cysts are being recognized with increasing frequency. Different modalities of treatment are discussed. The transcortical and transcallosal approaches are both effective techniques, but the latter is probably preferable in cases with mild ventricular dilatation.
Perceptual Style and Dual-Task Performance as a Function of Task Difficulty and Task Emphasis

Differences in dual-task performance by field-dependent and field-independent college students were investigated. The perceptual styles of the 102 subjects were determined by their performance on the Rod-and-Frame Test. Dual-task performance required the subjects to perform concurrently a central tracking task and a peripheral light-detection task. The effect of stress on dual-task performance was examined by employing three widely differing levels of tracking task difficulty. Three sets of instructions varied the relative importance of the two tasks within the dual-task situation. Both manipulation of task difficulty and instructional set had powerful effects on performance. However, performance differences among subjects with differing perceptual styles were found only on the central tracking task, with field-independent subjects consistently outperforming field-dependent ones. The results are discussed in terms of the theoretical basis for the perceptual style of field-dependence/field-independence as ...
Buoyant surface discharges into unsteady ambient flows

Abstract The dynamics of buoyant surface discharges into unsteady ambient crossflows have been studied in a schematic experiment, simulating the specific case of tidally reversing flows. The time evolution of the discharge is shown to be uniquely related to the jet-to-unsteady-crossflow scale measures: a length scale L u = (M 0 /| d u a / d t|) 1 3 and time scale T u = (M 0 /| d u a / d t| 4 ) 1 6 which relate the discharge momentum flux M0 to the reversal rate of the ambient dna/dt. The experiments show that jet parameters, such as the buoyancy build-up around reversal and the unsteady trajectory deflection, can be represented in a reasonably self-similar fashion if these scales are used for normalization.
Pharmacokinetics of Intraperitoneal, Intravenous, and Subcutaneous Recombinant Human Erythropoietin in Patients on Continuous Ambulatory Peritoneal Dialysis

The pharmacokinetics of recombinant human erythropoietin (Epo) were compared after mean single 99.1 U/kg intraperitoneal (IP), intravenous (i.v.), and subcutaneous (SC) doses in eight noninfected patients on peritoneal dialysis in a randomized, three-way, cross-over fashion. Continuous ambulatory peritoneal dialysis was performed in all patients on the days of the study. The IP dose was instilled into an empty peritoneum; total dwell time was 10 hours (4 hours dry, 6 hours with 2 L of peritoneal dialysis fluid). Blood samples were collected for 96 hours following IP and SC Epo, and for 72 hours following i.v. Epo. For the IP dose, a 10-hour effluent dialysate sample was collected to determine Epo recovery. Enzyme immunoassay was used for Epo analysis. The mean apparent volume of distribution was 0.05 L/kg, equivalent to 4.5% of total body weight; the mean total body clearance was 0.08 mL/min/kg. All eight patients exhibited multiexponential decay in serum Epo concentrations following i.v. Epo. Absorption of IP Epo was significantly greater than previous reports, presumably due to its administration into a dry peritoneum. The maximum concentrations following the IP and SC doses were nearly identical, but amounted to only 5% of the maximum concentrations for the i.v. dose. Subcutaneous Epo took nearly twice as long as IP Epo to achieve peak serum concentrations (17.1 +/- 5.0 hours v 9.4 +/- 1.9 hours). Compared with the IP route, the SC dose achieved a higher area under the serum concentration time curve from time 0 to 96 hours (AUC0-96; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
An optimization approach to multiple sequence alignment

Abstract The problem of multiple sequence alignment is recast as an optimization problem using Markov decision theory. One seeks to minimize the expected or average cost of alignment subject to data-derived constraints. In this setting, the problem is equivalent to a linear program which can be solved efficiently using modern interior-point methods. We present numerical results from an implementation of the algorithm for protein sequence alignment
Mitochondrial mechanisms and neurological disorders.

It is increasingly recognized that altered mitochondrial function can contribute to the pathobiology of many neurologic diseases. This special issue of Neurotherapeutics provides a critical review of recent developments in this area. Mitochondria play an important role in oxidative phosphorylation and energy production. Myriad disorders result from impaired energy production in both children and adults. Mitochondrial disorders are often very difficult to recognize, diagnose, and treat. In part, this relates to the marked clinical variability of such disorders, which involve multiple organ systems. Over the past 20 years there have been marked advances in the understanding of mitochondrial genetics, as well as mitochondrial changes that contribute to neurologic disease states. In addition, the variability of clinical phenotype has been underscored, along with the recognition that mitochondrial disorders may present differently in children and adults. This issue includes 11 critical reviews written by leading authorities in mitochondrial disease. The first section provides descriptive reviews of mitochondrial disorders and their clinical characteristics. Saneto et al. (see pages XXX), describe mtDNA-encoded disorders in children, Goldstein et al. (see pages XXX) discuss nuclear encoded disorders, and El-Hattab and Scaglia (pages XXX) address mitochondrial depletion disorders. Adult-onset mitochondrial disorders are reviewed by Cohen (pages XXX), and counseling-related issues by Vento and Pappa (pages XXX). The second section reviews imaging biomarkers by Gropman (pages XXX) and diagnostic methods by Falk and Wong (pages XXX), including next generation sequencing methods. The final section addresses potential therapeutics, with articles by Wolfe (pages XXX), Kerr (pages XXX), and Hurko (pages XXX). The latter includes an overview of clinical trials and potential biological therapies. Space limitations did not permit a truly comprehensive review of this rapidly expanding field. Nonetheless, it is hoped that this publication may serve as an important reference issue that stimulates further research in this important area
The association between postload plasma glucose levels and 38-year mortality risk of coronary heart disease: the prospective NHLBI Twin Study.

Background Due to the paucity of direct evidence, we aimed to evaluate whether the association between postload plasma glucose levels (ppGlucose) and long-term risk of mortality from coronary heart disease was independent of or attributable to genes and common environment. Methods and Findings From the prospective National Heart, Lung, and Blood Institute (NHLBI) Twin Study, we included 903 middle-aged male twins, who were nondiabetic, free of coronary heart disease at baseline (1969–1973), and followed for up to 38 years for coronary heart, cardiovascular, and all-cause mortality. Frailty survival models were used to estimate hazard ratio (HR) for various associations: overall (equivalent to singleton population association), within-pair (controlling for genes and environment common to co-twins), and between-pair association (reflecting influences of common factors). Overall associations were statistically significant for coronary heart and cardiovascular but not all-cause deaths after controlling for known risk factors. The associations were not statistically significant in within-pair analyses. The within-pair association was not statistically different by zygosity for specific and all-cause death risk. After the full adjustment for known risk factors, HR (95% confidence interval) for within-pair association was 1.07 (0.90, 1.28), 1.06 (0.94, 1.19), and 0.99 (0.94, 1.05) for coronary heart, cardiovascular, and all-cause mortality, respectively. The fully adjusted between-pair associations were statistically significant for specific and all-cause death risk: a 50 mg/dL increase in the mean value of ppGlucose for a twin pair was associated with a raised death risk [HR (95% confidence interval) 1.15 (1.02, 1.30), 1.10 (1.02, 1.20), and 1.05 (1.01, 1.09) for coronary heart, cardiovascular, and all-cause mortality, respectively]. Between-pair association was significant in dizygotic but not in monozygotic twins. Conclusion The positive association between ppGlucose and long-term coronary heart mortality risk is largely explained by factors shared between co-twins, including familial factors; however, within-pair effects cannot be absolutely excluded.
Plasmodium Circumsporozoite Protein Promotes the Development of the Liver Stages of the Parasite

Summary The liver stages of malaria are clinically silent but have a central role in the Plasmodium life cycle. Liver stages of the parasite containing thousands of merozoites grow inside hepatocytes for several days without triggering an inflammatory response. We show here that Plasmodium uses a PEXEL/VTS motif to introduce the circumsporozoite (CS) protein into the hepatocyte cytoplasm and a nuclear localization signal (NLS) to enter its nucleus. CS outcompetes NFκB nuclear import, thus downregulating the expression of many genes controlled by NFκB, including those involved in inflammation. CS also influences the expression of over one thousand host genes involved in diverse metabolic processes to create a favorable niche for the parasite growth. The presence of CS in the hepatocyte enhances parasite growth of the liver stages in vitro and in vivo. These findings have far reaching implications for drug and vaccine development against the liver stages of the malaria parasite.
Strain Rate Imaging Differentiates Hypertensive Cardiac Hypertrophy from Physiologic Cardiac Hypertrophy (Athlete’s Heart)

Background This study sought to determine whether strain rate imaging could distinguish between individuals with hypertensive left ventricular hypertrophy (LVH) and those with strength-training athletic LVH. Methods In all, 108 participants (30 hypertensive LVH, 30 strength-training LVH, 48 control) were enrolled. In addition to a baseline echocardiogram, strain, peak systolic strain rate (SR S ), peak early diastolic strain rate (SR E ), and peak late diastolic strain rate values were compared in the apical 4-chamber view. Results Athletes had no significant differences in strain, SR S , SR E , or peak late diastolic strain rate compared with control subjects ( P = .11, .99, .85, and .09, respectively). Individuals with hypertensive LVH had significantly decreased strain, SR S , and SR E (−16.8 ± 3.2%, −0.99 ± 0.15 s −1 , and 1.54 ± 0.40 s −1 , respectively) compared with control subjects (−21.7 ± 3.5%, −1.31 ± 0.27 s −1 , and 2.35 ± 0.57 s −1 , respectively; all P Conclusion Hypertensive LVH has significant longitudinal strain, SR S , and SR E reductions versus control. The lack of these reductions in athletes suggests that strain rate imaging may have clinical use in discerning the physiologic LVH state.
The Effect of Echinacea (Echinacea purpurea Root) on Cytochrome P450 Activity in Vivo

Background Echinacea is a widely available over-the-counter herbal remedy. Tinctures of echinacea have been shown to inhibit cytochrome P450 (CYP) in vitro. The effect of echinacea (Echinacea purpurea root) on CYP activity in vivo was assessed by use of the CYP probe drugs caffeine (CYP1A2), tolbutamide (CYP2C9), dextromethorphan (CYP2D6), and midazolam (hepatic and intestinal CYP3A). Methods Twelve healthy subjects (6 men) completed this 2-period, open-label, fixed-schedule study. Caffeine, tolbutamide, dextromethorphan, and oral and intravenous midazolam were administered before and after a short course of echinacea (400 mg 4 times a day for 8 days) to determine in vivo CYP activities. Results Echinacea administration significantly increased the systemic clearance of midazolam by 34%, from 32 ± 7 L/h to 43 ± 16 L/h (P = .003; 90% confidence interval [CI], 116%-150%), and significantly reduced the midazolam area under the concentration-time curve by 23%, from 127 ± 36 μg · h/L to 102 ± 43 μg · h/L (P = .024; 90% CI, 63%-88%). In contrast, the oral clearance of midazolam was not significantly altered (P = .655; 90% CI, 75%-124%), 137 ± 19 L/h compared with 146 ± 71 L/h. The oral availability of midazolam after echinacea dosing was significantly increased (P = .028; 90% CI, 108%-153%), from 0.23 ± 0.06 to 0.33 ± 0.13. Hepatic availability (0.72 ± 0.08 versus 0.61 ± 0.16; P = .006; 90% CI, 73%-90%) and intestinal availability (0.33 ± 0.11 versus 0.61 ± 0.38; P = .015; 90% CI, 125%-203%) were significantly altered in opposite directions. Echinacea dosing significantly reduced the oral clearance of caffeine, from 6.6 ± 3.8 L/h to 4.9 ± 2.3 L/h (P = .049; 90% CI, 58%-96%). The oral clearance of tolbutamide was reduced by 11%, from 0.81 ± 0.18 L/h to 0.72 ± 0.19 L/h, but this change was not considered to be clinically relevant because the 90% CIs were within the 80% to 125% range. The oral clearance of dextromethorphan in 11 CYP2D6 extensive metabolizers was not affected by echinacea dosing (1289 ± 414 L/h compared with 1281 ± 483 L/h; P = .732; 90% CI, 89%-108%). Conclusions Echinacea (E purpurea root) reduced the oral clearance of substrates of CYP1A2 but not the oral clearance of substrates of CYP2C9 and CYP2D6. Echinacea selectively modulates the catalytic activity of CYP3A at hepatic and intestinal sites. The type of drug interaction observed between echinacea and other CYP3A substrates will be dependent on the relative extraction of drugs at hepatic and intestinal sites. Caution should be used when echinacea is coadministered with drugs dependent on CYP3A or CYP1A2 for their elimination. Clinical Pharmacology & Therapeutics (2004) 75, 89–100; doi: 10.1016/j.clpt.2003.09.013
The Potential of Youth Participation in Planning

The field of planning is increasingly recognizing youth as an important stakeholder group, and there are calls to directly involve youth in planning processes. Because youth are in many respects different from adults, the practice of youth participation needs special consideration. This article summarizes the findings from empirical studies of youth participation in terms of the impacts on the young participants and their communities, the capacity of youth to participate, and five lessons for effective practice. The literature review will help planners create meaningful opportunities for youth to have a voice in community and environmental affairs.
Strategic Anticipation and Adjustment: Ex Ante and Ex Post Information in Explaining Sanctions Outcomes

The outcomes of economic sanctions should not be explained by ex ante information that has already been discounted by the interested parties when they decided to initiate or resist economic coercion. Therefore, contrary to much of the existing literature, only ex post information becoming available after the occurrence of sanctions should explain their results. This logic of strategic anticipation and selection applies to interstate interactions generally, such as those pertaining to the success of deterrence policy and the outbreak of war.
A Peak Generator for Gas Chromatography

Photoelectric peak generator for repeated reproduction of gas chromatogram peaks while data recording and integration variables are systematically studied
Progressive oxidative damage in the central nervous system of a murine model for juvenile batten disease

Oxidative damage is a known contributor to the pathogenesis of neurodegenerative diseases. Juvenile Batten disease is a progressive neurodegenerative disorder of childhood that results from mutation in Cln3. We have performed an initial characterization of the oxidative burden throughout the CNS in a Cln3−/− mouse model for juvenile Batten disease. A survey of multiple regions of the Cln3−/− mouse brain revealed a specific reduction of total glutathione, a tripeptide antioxidant molecule, in the cerebellum. Further analysis revealed an increase in protein oxidation not only in the cerebellum but also in the thalamus and primary motor cortex. Additionally, the thalamus was found to have an increase in the amount of a potent antioxidant enzyme, manganese superoxide dismutase (MnSOD), which may be in response to an increase in deleterious superoxide radicals. Colocalization studies indicate that microglia are localized directly adjacent to neurons expressing MnSOD, indicating that microglial activation may be related to the observed oxidative damage. This study helps to provide an initial measure of regions within the CNS of Cln3−/− mice that are specifically affected by the loss of CLN3 function and may serve to identify at the neuroanatomical level, the sequence of events that plays a role in the pathogenesis and clinical course of juvenile Batten disease. © 2007 Wiley-Liss, Inc.
Quorum-Sensing Signal Synthesis by the Yersinia pestis Acyl-Homoserine Lactone Synthase YspI

The acyl-homoserine lactone molecular species (AHLs) produced by the Yersinia pestis AHL synthase YspI were identified by biochemical and physical/chemical techniques. Bioassays of extracts from culture supernatants of the recombinant YspI and wild-type Yersinia pestis showed similar profiles of AHLs. Analysis by liquid chromatography-mass spectrometry revealed that the predominant AHLs were N-3-oxooctanoyl-l-homoserine lactone and N-3-oxo-hexanoyl-l-homoserine lactone.