cssi/SciSciGPT-SciSciNet huggingface dataset:
Dependence on phenobarbital but not pentobarbital using drug-adulterated food.

Abstract A drug-adulterated food (DAF) method was used in an attempt to establish physical dependence on either pentobarbital or phenobarbital in male CF1 mice. The mice were acclimated to the control diet for four days and then assigned to treatment groups. Group I continued to receive the control diet; Group II received pentobarbital, 5 mg/g food, increased by 5 mg, daily, for 14 days; Group III received pentobarbital, 5 mg/g food, increased by 5 mg, daily, for 7 days; Group IV received pentobarbital, 10 mg/g food, increased by 10 mg, daily, for 7 days; Group V received phenobarbital at 2.5 mg/g food for 5 days and then 3.0 mg/g food for 2 days. During drug administration, all mice were monitored daily for signs of intoxication, change in body weight, and food consumption. At the end of the drug exposure period all mice received control diet and were observed for signs of withdrawal. Mice in Group II and Group IV demonstrated significant declines in body weight and food consumption and an apparent increase in the degree of intoxication but no signs of withdrawal. Group II mice demonstrated little sign of impairment during exposure to pentobarbital and no withdrawal syndrome was observed. Mice presented phenobarbital were found to exhibit a significant degree of intoxication and a withdrawal syndrome was demonstrated. The data suggest, with respect to the drug administration schedules used, that the DAF method was not suitable for the establishment of physical dependence on pentobarbital in mice.
Treatment 'mismatch' in early prostate cancer: do treatment choices take patient quality of life into account?

BACKGROUND. Pretreatment urinary, bowel, and sexual dysfunction may increase the toxicity of prostate cancer treatments or preclude potential benefits. Using patient-reported baseline dysfunction from a prospective cohort study, we determined the proportion of patients receiving relatively contraindicated (‘mismatched’) treatments. METHODS. Baseline obstructive uropathy and bowel dysfunction relatively contraindicate brachytherapy (BT) and external beam radiation therapy (EBRT), respectively, because they increase patients' vulnerability to treatment-related toxicity. Baseline sexual dysfunction renders moot the intended benefit of nerve-sparing radical prostatectomy (NSRP), which is to preserve sexual function. We categorized patients' clinical circumstances by increasing complexity and counted the mismatches in each, expecting weaker or multiple contraindications to increase mismatched treatments. RESULTS. Of 438 eligible patients, 389 (89%) reported preexisting dysfunction, and more than one-third received mismatched treatments. Mismatches did not significantly increase with clinical complexity, and watchful waiting was very infrequent, even when all treatment options were contraindicated. Patient age and comorbidity, but not preexisting dysfunction, were associated with treatment choice. As expected, mismatched BT and EBRT led to worsened urinary and bowel symptoms, respectively, and NSRP did not improve outcomes after baseline sexual dysfunction. CONCLUSIONS. Pretreatment dysfunction does not appear to reliably influence treatment choices, and patients receiving mismatched treatments had worse outcomes. Further study is needed to determine why mismatched treatments were chosen, including the role of incomplete patient-physician communication of baseline dysfunction, and whether using a validated questionnaire before treatment decision-making would bypass this difficulty. Treatment mismatch may be a useful outcome indicator of the quality of patient-centered decisions. Cancer 2008. © 2007 American Cancer Society.
Remarks on Smalligan Marusic’s Comments

The author defends attributing to Berkeley the thesis that we can't conceive of extension in a mind-independent body against criticism from Smalligan Marusic. The author also specifies the resemblance requirements that Berkeley places on conceivability, concedes that the principle that ideas can only be like other ideas is not, strictly speaking, a premise in the Master Argument, and clarifies his views on the relation between possibility and conceivability.
Prostate cancer kills: Strategy to reduce deaths

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Estimation of molecular weights and Stokes' radii of polypeptide chains by thin-layer gel filtration in guanidine hydrochloride

Abstract A procedure for thin-layer gel filtration in 6 M guanidine hydrochloride has been developed and evaluated with a number of well-characterized proteins. Using Sephadex G-200, the linear fractionation range under these conditions is from 70,000 to 12,000 daltons, although the exact limits have not been defined. The technique affords a simple rapid procedure of high resolving power for evaluating the subunit composition and subunit molecular weights of proteins, using very small amounts (50 μg) of material. Since all proteins with reduced disulfide bonds behave as random coils in 6 M guanidine hydrochloride, the gel filtration migration rates and calculated Stokes' radii were found to be simple functions of their polymer lengths. This confirms the earlier observations of Fish et al. (6) with column gel filtration in the same solvent system.
A user-friendly self-similarity analysis tool

The concepts of self-similarity, fractals, and long-range dependence (LRD) have revolutionized network modeling during the last decade. However, despite all the attention these concepts have received, they remain difficult to use by non-experts. This difficulty can be attributed to a relative complexity of the mathematical basis, the absence of a systematic approach to their application and the absence of publicly available software. In this paper, we introduce SELFIS, a comprehensive tool, to facilitate the evaluation of LRD by practitioners. Our goal is to create a stand-alone public tool that can become a reference point for the community. Our tool integrates most of the required functionality for an in-depth LRD analysis, including several LRD estimators. In addition, SELFIS includes a powerful approach to stress-test the existence of LRD, Using our tool, evidence are presented that the widely-used LRD estimators can provide misleading results. It is worth mentioning that 25 researchers have acquired SELFIS within a month of its release, which clearly demonstrates the need for such a tool.
Bleeding on probing and probing depth as indicators of the response to plaque control and root debridement

19 adult periodontitis patients were treated with plaque control and a single episode of root debridement. Results of this treatment were monitored in non-molar sites, molar flat surface sites, and molar furcation sites by probing attachment level measurements every 3rd month for 24 months. After 24 months, sites with probing attachment loss were identified using linear regression analysis. Clinical scores for supragingival plaque, bleeding on probing, suppuration on probing, and probing depth, obtained from these sites during the 24-month study, were analyzed to determine if they could be used diagnostically as indicators of probing attachment loss. The results demonstrated that the diagnostic accuracy for these clinical indicators was generally low at all 3 anatomical site locations. A possible explanation for this limited diagnostic accuracy may be that some areas of probing attachment loss following basic periodontal therapy are caused by factors other than the progression of an inflammatory periodontal disease of microbial etiology.
Agreement between spectral-domain and time-domain OCT for measuring RNFL thickness

Background/aims: To evaluate spectral-domain (SD) optical coherence tomography (OCT) reproducibility and assess the agreement between SD-OCT and Time-Domain (TD) OCT retinal nerve fibre layer (RNFL) measurements. Methods: Three Cirrus-SD-OCT scans and one Stratus-TD-OCT scan were obtained from Diagnostic Innovations in Glaucoma Study (DIGS) healthy participants and glaucoma patients on the same day. Repeatability was evaluated using Sw (within-subject standard deviation), CV (coefficient of variation) and ICC (intraclass correlation coefficient). Agreement was assessed using correlation and Bland–Altman plots. Results: 16 healthy participants (32 eyes) and 39 patients (78 eyes) were included. SD-OCT reproducibility was excellent in both groups. The CV and ICC for Average RNFL thickness were 1.5% and 0.96, respectively, in healthy eyes and 1.6% and 0.98, respectively, in patient eyes. Correlations between RNFL parameters were strong, particularly for average RNFL thickness (R 2 = 0.92 in patient eyes). Bland–Altman plots showed good agreement between instruments, with better agreement for average RNFL thickness than for sectoral RNFL parameters (for example, at 90 µm average RNFL thickness, 95% limits of agreement were −13.1 to 0.9 for healthy eyes and −16.2 to −0.3 µm for patient eyes). Conclusions: SD-OCT measurements were highly repeatable in healthy and patient eyes. Although the agreement between instruments was good, TD-OCT provided thicker RNFL measurements than SD-OCT. Measurements with these instruments should not be considered interchangeable.
Phase Field Modeling of Ferroelectric Domain Wall Interactions With Charge Defects

The overall objective of this work is to develop a theoretical model that can track the evolution of the domain structures in ferroelectric crystals, which are responsible for the non-linear electromechanical behavior of these materials. To this end, a continuum thermodynamics framework is devised, and the theory falls into the class of phase-field or diffuse-interface modeling approaches. Here a set of micro-forces and governing balance laws are postulated and applied within the second law of thermodynamics to identify the appropriate material constitutive relationships. The approach is shown to yield the commonly accepted Ginzburg-Landau equation for the evolution of the polarization order parameter. Within the theory a form for the free energy is postulated that can be applied to fit the general elastic, piezoelectric and dielectric properties of a ferroelectric material near its spontaneously polarized state. Thereafter, a principle of virtual work is specified for the theory and is implemented to devise a finite element formulation. The theory and numerical methods are used to investigate the interactions of 180° and 90° domain walls with an array of charge defects and to determine the electromechanical pinning strength of the array on the walls.Copyright © 2006 by ASME
Temperature dependence of copolymerization

Copolymerization rate constant ratios have been determined as a function of temperature for the monomer pairs: styrene-acrylonitrile and dichlorostyrene-acrylonitrile. The temperature dependence, which represents the difference of the activation energies of the respective addition reactions, is of the magnitude expected, except for the styrene-dichlorostyrene system.
Is robotic hemithyroidectomy comparable to its conventional counterpart

Background We aimed to examine the outcomes of robot transaxillary thyroidectomy when compared with conventional thyroidectomy in a patient population that lacked the desire for a cervical incision. Methods A retrospective review of a prospectively collected database identified all patients who underwent robotic transaxillary hemithyroidectomy between April 2010 and February 2013. The outcomes of these patients were compared with a matched sample of consecutive patients who underwent conventional hemithyroidectomy during the same period. All values are expressed as mean ± standard error of mean. Results During the study period, 110 patients underwent robotic transaxillary hemithyroidectomy and were compared to a matched group of 110 patients who underwent conventional hemithyroidectomy. Both groups were similar in regard to body mass index ( P = .16) and volume of thyroid lobe resected ( P = .71). Patients offered the robotic approach were of younger age (46.4 ± 1 vs 51.9 ± 1.2 years; P P P > .05 for all). In the robotic group, 82.3% of patients were discharged on the same day of the procedure compared to 34.5% in the conventional group ( P Conclusion Robotic hemithyroidectomy is a safe and acceptable surgical approach for appropriately selected patients with thyroid disease. Further studies with prospective multicenter clinical trials will enable us to improve patient selection, techniques, and outcomes and to achieve better patient satisfaction.
Neurobiological Mechanisms of Language Acquisition

In this paper we specify language acquisition processes in terms of brain mechanisms in order to explain the variable success achieved by early and late language learners. On the basis of the literature in language acquisition, neurobiology, and linguistics, we propose a brain-based model for language acquisition. The model assumes two conditions must be met in order to acquire full knowledge of a particular language: first, that the learner is motivated to acquire the language; and second, that the learner is equipped with the ability to acquire grammatical knowledge. We explain the neural underpinnings for both motivation and grammatical ability and show how they interact to produce variable success in language acquisition.
The classification of deadlock prevention and avoidance is erroneous

Mechanisms to control resource deadlock are frequently classified as prevention or avoidance schemes. The prevention schemes are listed as those that directly negate the necessary preconditions of resource deadlock. The avoidance schemes, although they obviously also prevent deadlock, are described as not addressing the preconditions for the occurrence of deadlock.We claim that this classification is erroneous. Typically, the necessary preconditions for resource deadlock that are provided are incomplete. Once all of the preconditions are examined, it is obvious that "deadlock avoidance" does indeed negate a precondition.
A Meta-analysis of Heritability of Cognitive Aging: Minding the “Missing Heritability” Gap

The etiologies underlying variation in adult cognitive performance and cognitive aging have enjoyed much attention in the literature, but much of that attention has focused on broad factors, principally general cognitive ability. The current review provides meta-analyses of age trends in heritability of specific cognitive abilities and considers the profile of genetic and environmental factors contributing to cognitive aging to address the ‘missing heritability’ issue. Our findings, based upon evaluating 27 reports in the literature, indicate that verbal ability demonstrated declining heritability, after about age 60, as did spatial ability and perceptual speed more modestly. Trends for general memory, working memory, and spatial ability generally indicated stability, or small increases in heritability in mid-life. Equivocal results were found for executive function. A second meta-analysis then considered the gap between twin-based versus SNP-based heritability derived from population-based GWAS studies. Specifically, we considered twin correlation ratios to agnostically re-evaluate biometrical models across age and by cognitive domain. Results modestly suggest that nonadditive genetic variance may become increasingly important with age, especially for verbal ability. If so, this would support arguments that lower SNP-based heritability estimates result in part from uncaptured non-additive influences (e.g., dominance, gene-gene interactions), and possibly gene-environment (GE) correlations. Moreover, consistent with longitudinal twin studies of aging, as rearing environment becomes a distal factor, increasing genetic variance may result in part from nonadditive genetic influences or possible GE correlations. Sensitivity to life course dynamics is crucial to understanding etiological contributions to adult cognitive performance and cognitive aging.
Viking's Experiments and Hypothesis that Fe(VI) Is a Possible Candidate as a Martian Oxidant

In this rebuttal to G. Levin's critique of our previous publication, we claim again that iron(VI) is a very good candidate as a martian oxidant. Our experiments cannot be explained as a result of microbial activities, as we showed that Fe(VI) could be used as a sterilizing agent for destroying microorganisms, nucleic acids, and proteins.
Macromolecule transport in and effective pore size of ethanol pretreated human epidermal membrane

Abstract This study has examined the transport behavior of macromolecules of up to about 18 000 molecular weight (Mol. Wt) and the feasibility of using the theory of restricted diffusion of molecules through cylindrical pores to predict/characterize the pore sizes of synthetic membranes and ethanol pretreated human epidermal membrane (HEM). To minimize membrane and skin variabilities, experiments were conducted consecutively with each membrane using a two-chamber diffusion cell. Reference permeants or electrical resistance measurements were used to monitor possible membrane changes during a given set of runs. All HEM specimens exhibited the same pattern of significantly decreasing permeability with increasing polystyrene sulfonate (PSS) molecular weight. Previously obtained permeability data for ethanol pretreated HEM with polypeptides (leuprolide, CCK-8 and insulin) were found to be consistent with those for PSS; comparable permeability coefficients were observed for polypeptides and PSS's of comparable sizes. An analysis based on the theory of restricted diffusion for PSS transport across a synthetic Nuclepore® membrane yielded results consistent with the nomical pore size ( ∼ 75 A ) of this membrane. A similar analysis of the PSS data obtained with ethanol pretreated HEM yielded estimates of effective pore size for this membrane in the range, 22–54 A.
Beam Splitting Mirrors for an APS Beamline

We describe a set of two cooled mirrors used in tandem on a high-heat-load undulator beamline at the Advanced Photon Source (APS) to spatially split an incoming X-ray beam into two parts, allowing simultaneous operation on two beamlines. Such arrangements have the potential to increase beamline throughput by as much as a factor of two at a modest cost. Conceptual design, engineering analyses, and fabrication steps are outlined.
TU-D-BRB-07: Determination of Neutron Dose Due to a Therapeutic Proton Beam Incident On a Closed Tungsten MLC Using the Dual Hydrogenous/non-Hydrogenous Ionization Chamber Method

Purpose: To measure neutron dose around a tungstenMLC used for proton beam therapy using the dual ionization chamber (IC) method. Method and Materials:ICs were constructed with large 10cc volumes to enable low dose measurements in the mGy range. The chambers are identical aside from wall, electrode, and guard‐ring material with one constructed of A150 tissue‐equivalent plastic (T) and filled with methane based tissue‐equivalent gas and the other magnesium (U) and filled with argon gas. IC(T) has approximately the same sensitivity to neutrons and photons while the non‐hydrogenous IC(U) exhibits a lower sensitivity to neutrons. The dose from neutrons and photons can be expressed as DN=(RT‐RU)/(1‐kU) and DG=(RU‐ kURT)/(1‐kU) where RU,RT are IC readings and kU is the relative sensitivity of IC(U) to neutrons which varies with energy. Measurements were made with 230MeV proton beams incident on a closed MLC with the ICs on the beam axis 21cm from the MLC. Open field measurements were made with attenuation by 0, 0.5, 2, 5, 9, and 10cm of solid water. The ICs were calibrated against a Farmer chamber in air with a 6MV beam and suitable buildup caps. Results: Initial analysis of the measurements suggests an average neutron energy of 2.6MeV corresponding to kU=0.033. Measured neutron dose with the MLC closed and detector geometry stated above is 1.67mGy/Gy where IC(T) was used to determine dose in the open field. Conclusion: Initial measurements of neutron dose from a proton therapy beam incident on a MLC were performed which indicate the validity of the dual chamber method for determining neutron dose around a proton beam. This work was supported by the US Army Medical Research and Materiel Command under Contract Agreement No. DAMD17‐W81XWH‐07‐2‐0121. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the US Army.
Eastward-flowing bottom currents along the Clipperton Fracture Zone

Bottom currents were measured at four locations within a small area in the equatorial Pacific during a study of ocean floor erosion. The observed current speeds were low (<10 cm/sec) during the period of observation, and exhibited a strong semi-diurnal tidal component. In spite of the fluctuations in speed, the direction of flow at each location (eastward to northeastward) was remarkably uniform. The data suggest that there is a pronounced eastward-flowing bottom current along the north side of the Clipperton Fracture Zone, and that the fracture zone may therefore serve as a major barrier to the abyssal circulation in the central Pacific. This observation is consistent with previous studies of the regional circulation pattern.
Intelligence: Beyond a monolithic concept

The relationship of intelligence to biology has been ignored because the nervous system has been considered too difficult to comprehend. In this article we argue that the sources of human intelligence are biological in nature and are inherited from ancestral species. Segregated from biology, the concept of intelligence has inherent limitations as a monolithic construct. Viewed from a biological perspective, intelligence is the capacity of the central nervous system for self­ regulation under external (or stimulus-regulated), dynamic (or microsystem-regulated), and mind­ ful (or person-regulated) control. Current uses ofthe term "intelligence" are reminiscent ofWittgenstein's (1953) account of the concept of game. Intelligence is used interchangeably with competence, ex­ pertise, native talent, cultural talent, personal control, schooling, social interaction, and, of course, IQ. What is common to these various applications of the tenn "in­ telligence"? Only the spelling of the word itself. In the late 1970s , a similar problem haunted the literature on the notion of "schema," which was defined as the build­ ing block of cognition (RumeIhart, 1980) . Perhaps there are inherent limitations in the systematic use of monolithic concepts that otherwise serve us well in informal daily communication (lran-Nejad & Ortony, 1984) . Also problematic are definitions of monolithic con­ structs . For instance , Gardener (1986) defined intelligence as " an ability (or skill) to solve problems or to fashion products which are valued within one or more cultural settings" (p. 74). According to this definition, scientists such as Copernicus, Galileo, and Pasteur were not intel­ ligent because their solutions and products encountered ridicule and scorn. In this paper, we assume that there are three core ele­ ments of the concept of intelligence: (1) biology , (2) prob­ lem solving, and (3) survival. All other aspects of the con­ cept of intelligence (e.g., pedagogical, social, cultural, motivational, cognitive aspects) must be explained in terms of these core elements. Early approaches to the study of intelligence kept biology at a distance because the role of the nervous system is difficult to specify , a situation that we have addressed elsewhere (Iran-Nejad, Marsh, & Cle­ ments , in press). We believe that biology must be directly considered in the attempt to define intelligence , because the nervous system is innately biological, and it is the only known system capable of producing natural intelligence. Problem solving and survival, on the other hand , have historically been important components of theories of in­ telligence. Within the biological, evolutionary perspective, the sources of human intelligence are found in previous
SU‐E‐J‐35: A Model for the Simulation of EPID Measurements in the BeamNRC Monte Carlo Package

Purpose: The intent of this study was to create a virtual model of a simple Electronic Portal Image Device (EPID) in the BeamNRC Monte Carlo package which would simulate EPID measurements taken in vivo. Methods: A typical accelerator was created in the BeamNRC software using published 6MV spectra from Mohan, et. al. and the basic head design of a Varian accelerator head. The particle fluence at the level of the mylar window was output into a planar ‘phase space’ file. The output of this accelerator was delivered to a phantom with a 1 mm thick slab of water acting as the detector array using the DosXYZ package. Additionally, the fluence from the same geometry was computed at the level of the virtualEPID (vEPID). The simulations were run for 2×2, 5×5, 10×10, 20×20, and 25×25 field sizes, as well as a simple IMRT field. The results of the open field simulations were then used for the parameterization of a deconvolution kernel using the form described by Renner, et. al.. Results: The simulations were run with sufficient histories to produce a 1% uncertainty in the resulting fluence and dose matrices in the high dose/fluence region of the output. Additional software was created to convert ‘phase space’ files to fluence in the same grid as the vEPID. A final software package was written to iteratively determine the exponential fitting parameters described in Ritter, et. al. to deconvolve the detector function from the fluence measurements. Conclusions: The system will allow one to simulate both EPID measurements, as well as remove the detector function from vEPIDsimulations for further use in fluence studies using BeamNRC. This will allow one to simulate a system for in vivo patient measurements using an EPID to study without the need for time on a medical accelerator, and without contributing additional radiation fatigue to the EPID device.
Phase diagram based description of the hysteresis behavior of shape memory alloys

Abstract In this paper, we develop a consistent mathematical description of martensite fraction evolution during athermal thermoelastic phase transformation in a shape memory alloy (SMA) induced by a general thermomechanical loading. The global kinetic law is based on an experimentally defined stress–temperature phase diagram, transformation functions for a one-dimensional SMA body and a novel vector hysteresis model. The global kinetic law provides the phase fraction history given a loading path on the stress–temperature phase diagram and an initial value of martensite fraction. The phase transformation is considered to occur only within transformation strips on the phase diagram and only on loading path segments oriented in the transformation direction. The developed procedure can be used to model a range of different SMA transformation behaviors depending on the choice of transformation functions and local kinetic law algorithms. The phase fraction evolution is examined for a number of characteristic examples, including cyclic loading resulting in oscillatory transformation paths, and internal loops of partial transformation with associated attractor loops. Differences between the various local kinetic law algorithms used in the overall framework are highlighted. The simulation results using a cosine transformation function are found to be in excellent agreement with experimental data.
Regional Preferences for Interlocking Directorates among the Largest American Corporations

The phenomenon of corporate interlocks among large American corporations is examined in the context of an information network. This information network is analyzed at the regional level by use of multidimensional scaling. Three characteristics used in the selection of directors are revealed; the length of service of the chief executive officer, whether the region is a traditional manufacturing region, and whether the region of the headquarters of a corporation is east or west of the Mississippi River. These factors help to explain the bias of the manufacturing belt for selection of directors within the belt, and may be a contributing cause of the decline of the region.
Encoding and Decoding of Overlapping Odor Sequences

Odors evoke complex responses in locust antennal lobe projection neurons (PNs)-the mitral cell analogs. These patterns evolve over hundreds of milliseconds and contain information about odor identity and concentration. In nature, animals often encounter many odorants in short temporal succession. We explored the effects of such conditions by presenting two different odors with variable intervening delays. PN ensemble representations tracked stimulus changes and, in some delay conditions, reached states that corresponded neither to the representation of either odor alone nor to the static mixture of the two. We then recorded from Kenyon cells (KCs), the PNs' targets. Their responses were consistent with the PN population's behavior: in some conditions, KCs were recruited that did not fire during single-odor or mixture stimuli. Thus, PN population dynamics are history dependent, and responses of individual KCs are consistent with piecewise temporal decoding of PN output over large sections of the PN population.
Monitoring water from space

AGU Chapman Conference on Remote Sensing of the Terrestrial Water Cycle; Kona, Hawaii, 19–22 February 2012 A Chapman Conference was convened to review the current state of satellite missions and their related research, as well as to identify future needs and directions. The water cycle components considered included soil moisture, precipitation, evapotranspiration, snow/ice, groundwater, and surface water. Remotely sensed data were certainly the focus of the meeting, but ancillary data and in situ resources were also discussed.
Three-wavelength light transmission technique to measure smoke particle size and concentration

This paper describes an optical technique and instrumentation for measuring the average particle size and mass concentration of smoke. Transmission through the smoke at three wavelengths (0.45 μm, 0.63 μm, and 1.00 μm) is measured using a white light source and a compact, three-wavelength detector assembly. Sizes and concentrations are then calculated from the transmission data using Mie theory. Graphs of the calculated Mie extinction coefficients are presented for several complex refractive indices. This three-wavelength optical technique was used to study smoke from a wood-tunnel fire, and the results are compared to those of other sizing techniques.
The Niche City Idea: How a Declining Manufacturing Center Exploited the Opportunities of Globalization

This article examines a small city that forged a global service industry niche. Its leaders aligned the temporality of its historic downtown with that of the international furniture industry to make it the world's primary furniture merchandising node. This article overviews the radical transformation of the downtown, describes the ‘choreography’ of the area, and considers what the author feels are the important wider implications of what is, on the surface, a deceptively odd case. The author suggests that, in engaging this specific strategy, this very unique city portends a more general type of post-industrial Niche City, a city that forges global centrality by creating an economic specialization in a specific segment of the global service economy.
STEROIDOGENIC FACTOR-1 mRNA EXPRESSION IN HUMAN TISSUES: BASIC AND CLINICAL IMPLICATIONS. ▴ 385

Steroidogenic Factor-1 (SF-1), a tissue-specific orphan nuclear receptor, is the mouse homologue of fushi tarazu factor-1 (FTZ-F1), first identified in Drosophila. SF-1, a global regulator of steroid hydroxylases in the mouse, is expressed in the steroidogenic tissues i.e. the adrenal cortices and gonads, in the ventromedial hypothalamic nucleus (VMH) and the anterior pituitary. A specific SF-1- responsive element is present in the promoter regions of the steroid hydroxylases. Mullerian inhibiting substance, and gonadotrophin genes. Targeted disruption of the SF-1 gene in the mouse established its essential role in the organogenesis of the adrenal glands, gonads and VMH. These “knock out” mice had male to female sex reversal and complete adrenal insufficiency. We recently cloned the human SF-1 cDNA by heterologous probing of a λgt 11 human fetal adrenal cDNA library from a 20-week old male fetus, using a 32P-labeled, 1068 bp mouse cDNA probe. A 3.1kb cDNA fragment was identified, purified, subcloned into a plasmid vector, and sequenced. Sequence analysis revealed an entire open reading frame and most of the 5′ and 3′ untranslated regions. Using our human SF-1 cDNA, we examined the distribution of SF-1 mRNA expression in human tissues. Northern blot analysis of human peripheral tissues revealed a single message size of 3.5 to 4 kb in the testes, ovaries and several peripheral lymphoid tissues, including peripheral circulating leukocytes. The highest SF-1 mRNA expression was seen in the spleen. Lymphoid cell lines of B cell lineage, including Burkitt's lymphoma, also contained SF-1 mRNA. Northern blot analysis of the human brain also revealed a message size of 3.5 to 4 kb, as well as a second message of 4.4 kb. The SF-1 mRNA concentration was highest in the caudate and subthalamic nuclei, however, SF-1 message was also present in the amygdala, hippocampus, corpus callosum and brain cortex. These data suggest that human SF-1 cDNA will be useful in studies of non X-linked congenital adrenal hypoplasia, gonadal dysgenesis syndromes and endocrine disorders involving dysregulation of steroidogenesis. In addition, SF-1 might play a role in human lymphocyte maturation and/or function. The widespread presence of SF-1 message in the central nervous system is intriguing, given the recently described in situ production and actions of neurosteroids in the brain.
Unidirectional surface plasmon polariton coupler in the visible using metasurfaces

We have theoretically investigated a metasurface as a unidirectional surface plasmon polariton (SPP) coupler. The structure can work over a broad bandwidth in the visible region.
State space representation of nerve excitation

SummaryWhile the Hodgkin-Huxley model may be useful for some gross large-scale phenomena of nerve excitation, a critical analysis using more recently available system theoretic analysis reveals major inconsistencies and inadequacies with several fundamental assumptions of Hodgkin and Huxley. We have stated that the original cable equations are not applicable in the submicroscopic domain of a molecular or ionic nature. This leads to a mapping error, in that real three-dimensional vector space features of a cylindrical cable are mapped onto a scalar one-dimensional space in the classic cable equation. Furthermore only symmetrical voltage clamp experiments have been done, in which the physical arrangement ignores any real space or time phasic features. The Hodgkin-Huxley approach to modeling the nerve impulse ignores the vector nature of current densities and potentials, as well as the phase problems inherent in any three-dimensional wave problem. Only when these vector and phase properties are recognized, could we hope to begin to relate the macroscopic neuro-physiologic observations with the submicroscopic quantum properties of lipid and lipid protein membranes in ionic aqueous environments. The Hodgkin-Huxley model of ionic events will remain an important one in the efforts to understand excitation phenomena. It might be considered in analogy to the Bohr atom model, which while incorrect in many details gave the right answer for certain (largely spectroscopic) data for extremely simple situations. Nevertheless the Bohr model of the atom directed scientists down the right avenues to the eventual development of modern quantum theory. One can hope that critical evaluation of both data and experiments will lead to additional experiments and eventually a more acceptable theory of nerve excitation.
Inhibition of the Class II HMG–CoA reductase of Pseudomonas mevalonii

There are two structural classes of HMG–CoA reductase, the third enzyme of the mevalonate pathway of isopentenyl diphosphate biosynthesis—the Class I enzymes of eukaryotes and the Class II enzymes of certain eubacteria. Structural requirements for ligand binding to the Class II HMG–CoA reductase of Pseudomonas mevalonii were investigated. For conversion of mevalonate to HMG–CoA the −CH3, −OH, and −CH2COO− groups on carbon 3 of mevalonate were essential for ligand recognition. The statin drug Lovastatin inhibited both the conversion of HMG–CoA to mevalonate and the reverse of this reaction. Inhibition was competitive with respect to HMG–CoA or mevalonate and noncompetitive with respect to NADH or NAD+. Ki values were millimolar. The over 104-fold difference in statin Ki values that distinguishes the two classes of HMG–CoA reductase may result from differences in the specific contacts between the statin and residues present in the Class I enzymes but lacking in a Class II HMG–CoA reductase.
ICP0 Antagonizes ICP4-Dependent Silencing of the Herpes Simplex Virus ICP0 Gene

ICP0 is a regulatory protein that plays a critical role in the replication-latency balance of herpes simplex virus (HSV). Absence of ICP0 renders HSV prone to establish quiescent infections, and thus cellular repressor(s) are believed to silence HSV mRNA synthesis when ICP0 fails to accumulate. To date, an ICP0-antagonized repressor has not been identified that restricts HSV mRNA synthesis by more than 2-fold. We report the unexpected discovery that HSV's major transcriptional regulator, ICP4, meets the criteria of a bona fide ICP0-antagonized repressor of viral mRNA synthesis. Our study began when we noted a repressive activity that restricted ICP0 mRNA synthesis by up to 30-fold in the absence of ICP0. When ICP0 accumulated, the repressor only restricted ICP0 mRNA synthesis by 3-fold. ICP4 proved to be necessary and sufficient to repress ICP0 mRNA synthesis, and did so in an ICP4-binding-site-dependent manner. ICP4 co-immunoprecipitated with FLAG-tagged ICP0; thus, a physical interaction likely explains how ICP0 antagonizes ICP4's capacity to silence the ICP0 gene. These findings suggest that ICP0 mRNA synthesis is differentially regulated in HSV-infected cells by the virus-encoded repressor activity embedded in ICP4, and a virus-encoded antirepressor, ICP0. Bacteriophage λ relies on a similar repression-antirepression regulatory scheme to “decide” whether a given infection will be productive or silent. Therefore, our findings appear to add to the growing list of inexplicable similarities that point to a common evolutionary ancestry between the herpesviruses and tailed bacteriophage.
Synthesis of nanostructured silica powders by a room temperature aerosol process

Nano-sized porous silica powders are synthesized by a room temperature aerosol process. Reactant mixing configuration, reactant temperature, and drying temperature effects on the physical and morphological features of these powders are studied by nitrogen adsorption and small angle xray scattering techniques. These silica powders have high specific surface areas up to 600 m2/g, and show narrowly confined mesoporous characteristics. The powders display some structural change with temperature. The morphological features are modeled as mass fractals by small angle x-ray scattering. Measured fractal dimensions are around 2.8, indicating diffusion limited growth processes.
Seizure patterns in young animals; significance of brain carbonic anhydrase. II.

SummaryThe relation between activity of brain carbonic anhydrase and susceptibility to various grades of seizure patterns has been studied in young rats by observations of the effects of acetazolamide. The percentage inhibition of carbonic anhydrase and of the reaction catalyzed by the enzyme is related to the suppression of tonic and clonic seizure patterns. It is suggested that brain carbonic anhydrase and its specific catalytic activity may be essential for the propagation of the seizure discharge. Low levels of enzyme activity may be sufficient for focal discharge and the induction of minor seizure patterns while a relatively high degree of activity may be required for the propagation of a generalized seizure discharge and the induction of a major tonic seizure.
Modulation of T-Cell Activation by Malignant Melanoma Initiating Cells

Highly immunogenic cancers such as malignant melanoma are capable of inexorable tumor growth despite the presence of antitumor immunity. Thus, only a restricted minority of tumorigenic malignant cells may possess the phenotypic and functional characteristics needed to modulate tumor-directed immune activation. Here we provide evidence supporting this hypothesis. Tumorigenic ABCB5(+) malignant melanoma initiating cells (MMICs) possessed the capacity to preferentially inhibit IL-2-dependent T-cell activation and to support, in a B7.2-dependent manner, induction of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs). Compared with melanoma bulk cell populations, ABCB5(+) MMICs displayed lower levels of MHC class I, aberrant positivity for MHC class II, and lower expression levels of the melanoma-associated antigens MART-1, ML-IAP, NY-ESO-1, and MAGE-A. Additionally, these tumorigenic ABCB5(+) subpopulations preferentially expressed the costimulatory molecules B7.2 and PD-1, both in established melanoma xenografts and in clinical tumor specimens. In immune activation assays, MMICs inhibited mitogen-dependent human peripheral blood mononuclear cell (PBMC) proliferation and IL-2 production more efficiently than ABCB5(-) melanoma cell populations. Moreover, coculture with ABCB5(+) MMICs increased the abundance of Tregs, in a B7.2 signaling-dependent manner, along with IL-10 production by mitogen-activated PBMCs. Consistent with these findings, MMICs also preferentially inhibited IL-2 production and induced IL-10 secretion by cocultured patient-derived, syngeneic PBMCs. Our findings identify novel T-cell modulatory functions of ABCB5(+) melanoma subpopulations and suggest specific roles for these MMICs in the evasion of antitumor immunity and in cancer immunotherapeutic resistance.
Sleep: a nourisher in life's feast?

Despite several decades of basic and clinical research, the functions of sleep remain largely unknown. While sleep is absolutely essential for promoting alertness during the day, the field remains divided on its role in other processes including learning and memory with some supporting and others repudiating such functions (1). In recent years, another livelier debate has emerged on the potential role of sleep in influencing future weight gain. More specifically, the question that has been posed is whether alterations in habitual sleep duration (curtailment or extension) ‘cause’ or predispose to an increase in body weight? The evidence chronicled in this issue of the journal by Marshall and colleagues addresses the question of whether sleep duration is a ‘causal’ factor for future weight gain, all other things being equal (2). Given the ever increasing prevalence of obesity, the focus of the review is timely and unquestionably relevant for clinical practice and public health. However, unlike some of the other risk factors that have been associated with obesity (e.g., excess caloric intake, sedentary lifestyle), causally implicating the extremes of sleep duration as an independent intermediary has proved to be challenging.
Dendritic cells cross-present latency gene products from Epstein-Barr virus-transformed B cells and expand tumor-reactive CD8(+) killer T cells.

Dendritic cells (DCs) are not targets for infection by the transforming Epstein-Barr virus (EBV). To test if the adjuvant role of DCs could be harnessed against EBV latency genes by cross-presentation, DCs were allowed to process either autologous or human histocompatibility leukocyte antigen (HLA)-mismatched, transformed, B lymphocyte cell lines (LCLs) that had been subject to apoptotic or necrotic cell death. After phagocytosis of small numbers of either type of dead LCL, which lacked direct immune-stimulatory capacity, DCs could expand CD8+ T cells capable of killing LCLs that were HLA matched to the DCs. Necrotic EBV-transformed, major histocompatibility complex (MHC) class I–negative LCLs, when presented by DCs, also could elicit responses to MHC class II–negative, EBV-transformed targets that were MHC class I matched to the DCs, confirming efficient cross-presentation of LCL antigens via MHC class I on the DC. Part of this EBV-specific CD8+ T cell response, in both lytic and interferon γ secretion assays, was specific for the EBV nuclear antigen (EBNA)3A and latent membrane protein (LMP)2 latency antigens that are known to be expressed at low levels in transformed cells. The induced CD8+ T cells recognized targets at low doses, 1–10 nM, of peptide. Therefore, the capacity of DCs to cross-present antigens from dead cells extends to the expansion of high affinity T cells specific for viral latency antigens involved in cell transformation.
The human cytomegalovirus origin of DNA replication (oriLyt) is the critical cis-acting sequence regulating replication-dependent late induction of the viral 1.2-kilobase RNA promoter.

Abstract Plasmid constructs containing the 1.2-kb RNA promoter from the long terminal repeat region of human cytomegalovirus (HCMV) display the early-phase regulation of this promoter but lack the characteristic late induction (E. J. Wade, K. M. Klucher, and D. H. Spector, J. Virol. 66:2407-2417, 1992). To determine if the HCMV origin of replication (oriLyt) was necessary and sufficient for the late induction of the 1.2-kb RNA promoter, we cloned a 9.6-kbp segment of the origin of replication onto the p456 OCAT plasmid containing the 1.2-kb RNA promoter. This plasmid was designated ori456 OCAT. A control construct, which contains all of the same sequences as the ori456 OCAT construct except that a 2.4-kbp segment derived from HCMV EcoRI segment U is inverted in orientation to disrupt the origin function, was designated inv456 OCAT. After electroporation into human fibroblast cells and infection with HCMV 24 h later, ori456 OCAT replicated and showed the same early and late transcription pattern as the authentic viral 1.2-kb RNA. Under similar conditions, the inv456 OCAT neither replicated nor showed late induction. Experiments using plasmids synthesized in bacteria lacking methylation activity demonstrated that the late induction was not dependent on the change in methylation state of the plasmids. Ganciclovir, an inhibitor of the HCMV DNA polymerase, was used to demonstrate the replication dependence of the expression of the virally encoded 1.2-kb RNA, while the nearby early 2.7-kb RNA was unaffected. Ganciclovir also inhibited the late induction of the chloramphenicol acetyltransferase gene from ori456 OCAT, while expression from inv456 OCAT increased. Site-specific mutations in two previously identified important regulatory elements of the 1.2-kb RNA promoter, the AP1-binding site and the CATA site, indicated that these sites continue to contribute to promoter activity at late times but that the replication-dependent late induction acts independently of these sites. Possible mechanisms underlying the late induction are discussed.
Evaluation of the AnaeroPack system for growth of anaerobic bacteria.

Growth of anaerobic bacteria in the AnaeroPack (Mitsubishi Gas Chemical America, Inc., New York, N.Y.) anaerobic atmosphere generation systems, both the AnaeroPack jar and pouch and the AnaeroPack in a GasPak jar were considered equivalent to or better than growth obtained in the corresponding GasPak jar or pouch system (Becton Dickinson Microbiology Systems, Cockeysville, Md.) for 89 (86%) of the 103 anaerobes tested. There were a total of 26 discrepancies after 48 h of incubation, with 16 discrepancies unresolved after 96 h of incubation. The AnaeroPack jar and pouch never failed to reduce the anaerobic indicator. The AnaeroPack systems are easy to use and performed at least as well as or better than the BBL GasPak systems for growth of anaerobic bacteria.