cssi/SciSciGPT-SciSciNet huggingface dataset:
Molecular enzymology of 5-Aminolevulinate synthase, the gatekeeper of heme biosynthesis

Pyridoxal-5'-phosphate (PLP) is an obligatory cofactor for the homodimeric mitochondrial enzyme 5-aminolevulinate synthase (ALAS), which controls metabolic flux into the porphyrin biosynthetic pathway in animals, fungi, and the α-subclass of proteobacteria. Recent work has provided an explanation for how this enzyme can utilize PLP to catalyze the mechanistically unusual cleavage of not one but two substrate amino acid α-carbon bonds, without violating the theory of stereoelectronic control of PLP reaction-type specificity. Ironically, the complex chemistry is kinetically insignificant, and it is the movement of an active site loop that defines kcat and ultimately, the rate of porphyrin biosynthesis. The kinetic behavior of the enzyme is consistent with an equilibrium ordered induced-fit mechanism wherein glycine must bind first and a portion of the intrinsic binding energy with succinyl-Coenzyme A is then utilized to perturb the enzyme conformational equilibrium towards a closed state wherein catalysis occurs. Return to the open conformation, coincident with ALA dissociation, is the slowest step of the reaction cycle. A diverse variety of loop mutations have been associated with hyperactivity, suggesting the enzyme has evolved to be purposefully slow, perhaps as a means to allow for rapid up-regulation of activity in response to an as yet undiscovered allosteric type effector. Recently it was discovered that human erythroid ALAS mutations can be associated with two very different diseases. Mutations that down-regulate activity can lead to X-linked sideroblastic anemia, which is characterized by abnormally high iron levels in mitochondria, while mutations that up-regulate activity are associated with X-linked dominant protoporphyria, which in contrast is phenotypically identified by abnormally high porphyrin levels. This article is part of a Special Issue entitled: Pyridoxal Phosphate Enzymology.
Thermal hydraulic characterization of stainless steel wicks for heat pipe applications

Heat pipe design and manufacturing require the knowledge of the thermal hydraulic performance of the wicks. The aim of the present work is the thermal hydraulic characterization of stainless steel wicks (sintered porous media and gauzes) to be employed in our experimental water heat pipe. Commercial sintered porous media (able to capture 90 % of 90 μm particles and 99.9 % of 130 μm particles) and gauzes (nominal wire size 0.11 mm, square mesh opening 0.209 mm) have been used. Thermal hydraulic characterization of the wicks is obtained through the experimental measurement of: capillary height (through which the equivalent porous radius can be evaluated), liquid hydraulic head (through which the liquid pressure drop in the wick is evaluated) wick permeability is also evaluated from the hydraulic head (through Darcy's law), heat flux, wick mass flow rate during the evaporation (through which, from the knowledge of other measured wick parameters, the wick two-phase pressure drop is calculated) and wick porosity (through which the thermal conductivity of the wick saturated with liquid can be determined). Concerning the heat flux, it is found to be dependent on the distance between the liquid level and the evaporating zone, the evaporating zone length, the wall superheat and the water subcooling, the contact between the heater and the wick and the superficial boundary conditions of the wick.
The Optical Constants of Crystals of Selenium and Tellurium for Wave-Lengths from 3000 to 5000 Angstroms

The measurements were made by a photographic method, for two positions of the crystal, (1) with the optic axis parallel, and (2) with the axis perpendicular to the plane of incidence. Two sets of optical constants were found for each substance. For selenium, in the parallel position the index of refraction was found to vary from 3.4 to 4.4, and the reflecting power from 0.38 to 0.46; in the perpendicular position the index varies from 2.3 to 3.1, and the reflecting power from 0.41 to 0.34. For tellurium, in the parallel position the index varies from 1.9 to 2.9, and the reflecting power from 0.10 to 0.27; in the perpendicular position the index varies from 1.7 to 2.7, the reflecting power from 0.09 to 0.23. The average error is estimated to be about 5 per cent. The accuracy is greatest for the middle range of wavelengths, 3500-4000 A.
Dithienopyrrole–quinoxaline/pyridopyrazine donor–acceptor polymers: synthesis and electrochemical, optical, charge-transport, and photovoltaic properties

Soluble alternating copolymers of N-(3,4,5-tri-n-dodecyloxyphenyl)dithieno[3,2-b:2′,3′-d]pyrrole donor groups and 2,3-di-n-decylquinoxaline, 2,3-di-n-decylpyrido[3,4-b]pyrazine, 2,3,6,7-tetrakis(n-decyloxy)benzo[a,c]phenazine, or 2,3,6,7-tetrakis(n-decyloxy)dibenzo[f,h]pyrido[4,3-b]quinoxaline acceptors were synthesised using Stille coupling reactions. Experimental absorption maxima in THF range from 645 to 770 nm. These optical data, along with the results of quantum-chemical calculations and electrochemical measurements, show that, as expected, the pyridopyrazine moiety acts as a stronger acceptor than quinoxaline and that the extended species benzophenazine and dibenzopyridoquinoxaline are stronger acceptors than quinoxaline and pyridopyrazine, respectively. Modest average hole mobilities of up to ca. 3.0 × 10−4 cm2 V−1s−1 were obtained in field-effect transistors. Bulk heterojunction photovoltaic devices made from blends of the benzo[a,c]phenazine-based polymer with 3′-phenyl-3′H-cyclopropa[1,9](C60-Ih)[5,6]fullerene-3′-butanoic acid methyl ester (1 : 3 weight ratio) exhibited average power conversion efficiencies up to 1.4%.
A multimodal data mining framework for soccer goal detection based on decision tree logic

In this paper, we propose a new multimedia data mining framework for the extraction of soccer goal events in soccer videos by utilising both multimodal analysis and decision tree logic. The extracted events can be used to index the soccer videos. We first adopt an advanced video shot detection method to produce shot boundaries and some important visual features. Then, the visual/audio features are extracted for each shot at different granularities. This rich multimodal feature set is then filtered by a pre-filtering step in order to clean the noise as well as to reduce the irrelevant data. A decision tree model is built upon the cleaned data set and is used to classify the goal shots. We also present the experimental results for the proposed framework, which indicate the performance of the framework for soccer goal extraction.
Co-occurrence texture feature variation for a moving window over apple images

Near infrared reflectance (NIR) images of bruised `Delicious' applies were converted to images of texture properties. Bruises of two sizes (11 mm and 26 mm diameter) and two ages (1 d and 90 d) were examined. Seven texture properties (variance, entropy, product moment, difference entropy, inverse difference, difference variance, and sum variance) were computed from a cooccurrence matrix. Window size and neighborhood distance for the cooccurrence matrix were set to optimize the texture contrast between bruised and unbruised tissue. The window position was incrementally scanned over the entire apple image creating a new image of texture values. Four neighborhood directions (0 degree(s), 90 degree(s), 45 degree(s), 135 degree(s)) were considered. Sum variance was the only texture property that showed improved contrast of the bruised/unbruised areas relative to the original NIR image. All other texture properties produced images that highlighted the edge of the bruise. The variance property produced images with the best defined bruise edges irregardless of bruise size or age. Variance and sum variance show promise as additional features to the grey tone image for discriminating apple bruises.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Vanadate-resistant yeast mutants are defective in protein glycosylation.

Abstract Spontaneous recessive orthovanadate-resistant mutants of Saccharomyces cerevisiae were obtained in five complementation groups, and all show defects in protein glycosylation that mimic the previously isolated mnn mutants. Three of the groups are allelic to the known mnn8, mnn9, and mnn10 mutants, whereas the other two groups show other glycosylation defects. The vanadate-resistant phenotype was associated with enhanced hygromycin B sensitivity. The glycosylation phenotypes of the mutants are all reflections of defects in glycoprotein trafficking, and the easy isolation of vanadate-resistant or hygromycin B-sensitive mutants should facilitate the study of this process.
Wilson's disease.

Concepts concerning the cause and the pathogenesis of Wilson's hepatolenticular degeneration have undergone a slow and tortuous evolution. 49 Hints regarding the presence of excess copper in the tissues of a patient were obtained as early as 1913, 1 year after Wilson's publication, but Rumpel believed that silver was the principal toxin. 24 A decade later, ophthalmologists noted the similarity of Kayser-Fleischer rings and the copper-induced corneal rings encountered in patients with chalcosis but failed to appreciate the significance of these isolated observations. Only toward the middle of the century did Cumings 5 establish that Wilson's disease is the result of copper toxicity, concluding that removal of copper from the tissues may be therapeutic. At that time British Anti-Lewisite, 2,3-dimercaptopropanol (BAL) was the only chelating agent used to treat patients with neurologic Wilson's disease. A few years later, Scheinberg and Gitlin discovered the pathognomonic deficiency of ceruloplasmin in plasma. 26 Soon thereafter, Walshe introduced two oral therapies: first penicillamine, and later trientine, which revolutionized patient management and drastically improved the prognosis of patients diagnosed before irreversible damage to liver and brain had taken place. 44,45,47 Several years later, zinc salts were found to be effective in the management of certain patients. 2,33,50
Aminoglycoside Pharmacokinetic Parameters in Neurocritical Care Patients Undergoing Induced Hypothermia

Study Objective. To determine the effects of mild-to-moderate induced hypothermia—a neuroprotectant and/or therapeutic strategy for the management of intracranial hypertension in neurologically injured patients—on the pharmacokinetics of aminoglycoside therapy. Design. Pharmacokinetic analysis. Setting. Critical care unit at a university-affiliated hospital. Patients. Three patients, aged 22, 24, and 47 years, who received tobramycin and had documented tobramycin levels while undergoing induced hypothermia for more than 24 hours for intracranial hypertension. Measurements and Main Results. For each of the three patients, predicted pharmacokinetic parameters (volume of distribution, first-order elimination rate constant, half-life, and renal drug clearance) based on population data were compared with their actual pharmacokinetic parameters that were calculated based on observed tobramycin serum levels. All three patients had a normal creatinine clearance, estimated according to established methods. When pharmacokinetic parameters were calculated after the first tobramycin dose using a one-compartment method, all patients had a slower first-order elimination rate and a larger volume of distribution compared with predicted population estimates. Conclusion. These findings suggest that induced hypothermia may result in impaired elimination of aminoglycosides. Caution should be exercised when attempting to use predicted pharmacokinetic parameters to dose aminoglycosides in this patient population, and first-dose pharmacokinetics should be considered to optimize the dose and dosing interval early in the course of therapy. Further investigation of this phenomenon with greater numbers of patients are needed to confirm these findings and to determine optimal dosing strategies of aminoglycosides in patients undergoing induced hypothermia.
Constraints in distortion-invariant target recognition system simulation

Automatic target recognition (ATR) is a mature but active research area. In an earlier paper, we proposed a novel ATR approach for recognition of targets varying in fine details, rotation, and translation using a Learning Vector Quantization (LVQ) Neural Network (NN). The proposed approach performed segmentation of multiple objects and the identification of the objects using LVQNN. In this current paper, we extend the previous approach for recognition of targets varying in rotation, translation, scale, and combination of all three distortions. We obtain the analytical results of the system level design to show that the approach performs well with some constraints. The first constraint determines the size of the input images and input filters. The second constraint shows the limits on amount of rotation, translation, and scale of input objects. We present the simulation verification of the constraints using DARPA's Moving and Stationary Target Recognition (MSTAR) images with different depression and pose angles. The simulation results using MSTAR images verify the analytical constraints of the system level design.
Quantitative immunocytochemistry of GABA and synaptophysin in the cerebellar cortex of old ethanol-fed rats.

Background Ethanol-related synaptic loss, Purkinje neuron dendritic regression, and parallel fiber degeneration have been reported in the molecular layer of the adult cerebellar cortex. The known plasticity of the cerebellar cortex suggests that this region may respond to ethanol-related losses by compensatory remodeling of cerebellar circuitry. Stellate and basket interneurons may play an essential role in the remodeling process. Little is known about ethanol-related effects on cerebellar interneurons or on the GABAergic synapses that they form despite the fact that ethanol-related alterations in these components may contribute to the sensitivity of the cerebellum to ethanol. The paucity of data on GABAergic synapses extends to other synaptic components as well including synaptophysin, a glycoprotein component of synaptic vesicles and a synaptic marker. Methods Thirty 12-month-old F 344 rats were divided into ethanol-fed, pair-fed, and chow-fed groups (10/group). Ethanol rats were treated for 40 weeks with a liquid diet in which 35% of the calories were derived from ethanol. At the end of treatment, rats were perfused, and tissue processed for quantitative immunohistochemistry of GABA and synaptophysin labels. Results Levels of GABA within inhibitory synapses formed by stellate and basket neurons and levels of synaptophysin were not altered by long-term ethanol treatment. Conclusions Stable levels of GABA within GABAergic basket and stellate interneuron synapses suggest that interneurons in the molecular layer of the cerebellar cortex may not play a major role in remodeling of cerebellar circuitry following long-term ethanol consumption. The lack of ethanol-related alterations in synaptophysin levels reported here suggests that synaptic vesicles may be relatively insensitive to ethanol and that known ethanol-related effects on synapse number are due to other mechanisms.
Management of Multiple Uavs with Imperfect Automation

Forty-two participants manipulated two or four unmanned aerial vehicles (UAVs) while monitoring an adjacent display for camouflaged tanks. They were sometimes supported in the tank-detection task by an automated target recognition system that operated at either a reliability of .9 with a threshold designed to provide an equal number of false-alarms and misses, .6 with a low threshold producing more automation false alarms, or .6 with a high threshold producing more automation misses. As taskload doubled, performance on the UAV task was significantly reduced. The effect was not mediated by the presence of automated aids, though the aids did influence performance in the tank-detection task. Tank detection was improved by both the highly-reliable aid and (to a lesser extent) by the miss-prone aid, but was not improved (and sometimes hurt) by the false-alarm prone condition. The results support the independence model of reliance and compliance proposed by Meyer (2001).
Visual correlation for situational awareness

We present a novel visual correlation paradigm for situational awareness (SA) and suggest its usage in a diverse set of applications that require a high level of SA. Our approach is based on a concise and scalable representation, which leads to a flexible visualization tool that is both clear and intuitive to use. Situational awareness is the continuous extraction of environmental information, its integration with previous knowledge to form a coherent mental picture, and the use of that picture in anticipating future events. In this paper we build on our previous work on visualization for network intrusion detection and show how that approach can be generalized to encompass a much broader class of SA systems. We first propose a generalization that is based on what we term, the w/sup 3/ premise, namely that each event must have at least the what, when and where attributes. We also present a second generalization, which increases flexibility and facilitates complex visual correlations. Finally, we demonstrate the generality of our approaches by applying our visualization paradigm in a collection of diverse SA areas.
Experiential connectedness in children's attachment interviews: An examination of natural word use

Attachment classification derived from narrative analysis is widely used as a marker of psychological organization. In contrast to this top-down approach, bottom-up, word count–based analyses of narratives are also used to measure psychological states. The current study integrates these 2 approaches by examining their overlap in 93 school-aged children. Participants completed the Child Attachment Interview; transcriptions of this interview were subjected to word count–based linguistic analysis. Compared with secure children, dismissing children showed less and preoccupied children showed more signs of experiential connectedness. Disorganized children decreased in experiential connectedness during loss discussions and used more words related to death during nonloss sections of the interview. Results are discussed in terms of their relevance to attachment and relationship research. The internal working model of attachment (IWM; Bowlby, 1980), a person’s characteristic relationship schema that develops from interactions with primary caregivers, is widely studied as a factor underlying relational and mental health (Bakermans-Kranenburg & van IJzendoorn, 2009). The field of attachment has a long history of assessing the IWM via narrative discourse. Among adults, IWMs are typically studied using the Adult Attachment Interview (AAI; George, Kaplan, & Main, 1996), and a large body of evidence suggests that coding patterns of discourse yield
Have We Forgotten the Purpose of Phase III Studies

Experimental design of cancer therapeutics involves wellaccepted phases designed to establish safe dosing, assess efficacy, and determine relative effectiveness compared with standard regimens. Phase I testing allows identification of tolerable dosing and an administration schedule that is followed by phase II testing in a specific disease to examine safety and early efficacy. If acceptable toxicity and efficacy is observed in phase II testing, development may proceed down two different pathways to obtain regulatory approval for marketing within the United States. One pathway involves performance of phase III study(s) comparing the respectivenewagentwiththeacceptedstandardtreatment.Thisrandomized phase III design provides the best opportunity to examine patientbenefitwithrespecttoimprovementinremissionduration, survival, and disease symptoms along with early and late toxicities associated with each treatment. The second pathway is most appropriateforuseinconditionswherenogoodstandardoralternative therapy exists. These single-arm phase II studies are of sufficient size to adequately assess patient safety and provide evidence of patient benefit. However, this nonrandomized design lacks a control comparison, thereby introducing biases that can overestimatethebenefitofthetherapeuticagent.Asaconsequence
Transorbital target localization with augmented ophthalmologic surgical endoscopy.

Access to the space behind the eyeball is limited by the position of the globe anteriorly, the neurovascular structures embedded in fat posteriorly, and the tight bony confine of the orbit. These anatomical relationships have impeded application of minimally invasive procedures to the region, such as foreign body removal, tumor biopsy, or the administration of medical therapy directly to the optic nerve. An image-guided system was developed using a magnetically tracked flexible endoscope to navigate behind the eye, with the aim of enabling accurate transorbital surgery to user-specified target locations. Targets were defined by microspherical bulbs containing water or gadolinium contrast, with differing visible coloring agent. Six living pigs were anesthetized and two microspheres of differing color and contrast content were implanted in the fat tissue of each orbit. Preoperative T1-weighted MRI volumes were obtained and registered intraoperatively. The system capabilities were tested with a series of targeted surgical interventions. The surgeon was required to navigate the endoscope to each lucent microsphere and identify it by color. For three pigs, 3D/2D registration was performed such that the target’s image volume coordinates were used to display its location on real-time endoscope video. The ophthalmologic surgeon was able to correctly identify every target by color, with average intervention time of 24.2 min without enhancement and 3.2 min with enhancement. This difference is highly statistically significant $$(p < 0.02)$$ for reduction in localization time. Accurate transorbital target localization is possible in-vivo using image-guided transorbital endoscopy, while endoscopic enhancement through the use of video augmentation significantly reduces procedure time.
Magnetic shadowing of charged particles by an extended surface

The problem of particle shadowing by the lunar surface is examined. Shadow zones are obtained analytically for small-aperture detectors on an infinite flat surface and are shown to be in good agreement with those obtained by numerical trajectory tracing. The shadow zones cover about half of all possible external field orientations for a vertical detector, which may result in serious underestimations of the frequency of observation of a particular plasma region. Shadowing may cause wide variations between observed and actual pitch angle distributions even in the case of multiple- or large-aperture detectors. Since the particle flux can be considered approximately isotropic only for magnetic fields within 35 deg of the surface normal, the electron flux to the surface may be overestimated in current balance calculations ignoring the magnetic field direction. In addition, photoelectrons may be returned to the surface by the magnetic field.
A new typology of health behaviours for personality-health predictions: The case of locus of control

Psychological investigations of the impact of personality on health behaviours have tended to emphasize fine distinctions among personality variables while failing to distinguish among different ki...
Sensitivity analysis in cellular manufacturing system in the case of product mix variation

In this paper, performance measures such as mean flow time and work-in-process inventories will be used to determine the changes in the performance of a cellular manufacturing system due to product mix variations.
Central Venous Catheter Infections in Burn Patients with Scheduled Catheter Exchange and Replacement

Introduction Consensus in the general critical care patient population is that routine central venous catheter change is not necessary, and that central lines should not be rewired in the setting of possible infection. This concept has not carried over into the burn realm. In burn patients the rewiring of lines may lead to increased infection rates. Methods Fifty-nine consecutive critically ill burn patients requiring central line placement were included: 277 central lines and 1691 catheter days. Standard care protocol was followed in all patients, with lines being placed initially by new site insertion, changed over a guidewire on day 6, and moved to a new site on day 12. New sites were used for all suspected or documented line infections. All other care was the same. New site placements were compared to guidewire exchanges. Pediatric patients (under the age of 18) were considered with and separate from adults. Results There was no difference in the incidence of catheter-related bloodstream infections (CRBSI) between lines placed by new site access (15.4/1000 catheter days) or by guidewire exchange (15.4/1000). Considering the 979 pediatric line days, there was a distinct difference, with new sites having 16.6/1000, and rewires 25.2/1000. Adults revealed the opposite trend, rewires having no occurrences of CRBSI, and new sites 13.7/1000. Children had a higher rate of CRBSI, 19.4/1000 days, compared to adults at 9.8/1000 days. Children had larger burns (P Conclusions In pediatric patients guidewire exchange increased the incidence of infection. This was not noted in adult patients. The utility of guidewire exchange needs to be further investigated in adults, although this data would imply that it may be safe to use routine rewire of lines in adult burn patients. Pediatric patients require an increase in vigilance to minimize CRBSI. Central venous catheters should be removed as soon as not needed and routine change of lines in burn patients needs continued evaluation.
Activation of oxidative stress genes by mutations at the soxQ/cfxB/marA locus of Escherichia coli.

Exposure of Escherichia coli to superoxide-generating drugs, such as menadione or paraquat, uniquely induces approximately 40 proteins, nine of which are under the positive control of the soxR locus (at min 92). We report here that certain mutations at a separate locus that we have named soxQ (at min 34) confer some of the phenotypes seen in soxR-constitutive strains, including resistance to menadione. A previously known mutation called cfxB, identified through antibiotic resistance, is likely an allele of soxQ. The soxQ1 and cfxB mutations cause transcriptional activation of the genes that encode Mn-containing superoxide dismutase, glucose 6-phosphate dehydrogenase, and the soi-17/19::lac and soi-28::lac fusions. These genes are also activated by soxR, but the soxQ1 and cfxB mutations increase the synthesis of seven other proteins not influenced by soxR. Moreover, the soxQ1- and cfxB-dependent phenotypes do not depend on the soxR gene, and gene induction by soxR in response to redox stress does not depend on the soxQ locus. As well as increasing cellular resistance to some oxidants, the soxQ1 and cfxB mutations confer elevated resistance to various antibiotics, probably via diminished expression of outer membrane protein OmpF. The marA1 multiple-antibiotic resistance mutation (also at min 34) behaves like a weak allele of soxQ but probably resides in a nearby gene that, with soxQ, is part of a regulatory complex. We propose that soxQ helps control some oxidative stress proteins as part of another regulon that responds to an unknown environmental signal. Images
Spectral processing deficits in belt auditory cortex following early postnatal lesions of somatosensory cortex.

Abstract Induced or genetically based cortical laminar malformations in somatosensory cortex have been associated with perceptual and acoustic processing deficits in mammals. Perinatal freeze-lesions of developing rat primary somatosensory (S1) cortex induce malformations resembling human microgyria. Induced microgyria located in parietal somatosensory cortex have been linked to reduced behavioral detection of rapid sound transitions and altered spectral processing in primary auditory cortex (A1). Here we asked whether belt auditory cortex function would be similarly altered in rats with S1 microgyria (MG+). Pure-tone acoustic response properties were assessed in A1 and ventral auditory (VAF) cortical fields with Fourier optical imaging and multi-unit recordings. Three changes in spectral response properties were observed in both A1 and VAF in MG+ rats: 1) multi-unit response magnitudes were reduced 2) optical and multi-unit frequency responses were more variable; 3) at high sound levels units responded to a broader range of pure-tone frequencies. Optical and multi-unit pure-tone response magnitudes were both reduced for low sound levels in VAF but not A1. Sound level “tuning” was reduced in VAF but not in A1. Finally, in VAF frequency tuning and spike rates near best frequency were both altered for mid- but not high-frequency recording sites. These data suggest that VAF belt auditory cortex is more vulnerable than A1 to early postnatal induction of microgyria in neighboring somatosensory cortex.
China after Deng: Some perspectives∗

Deng Xiaoping's succession arrangement is different from the typical practice of the supreme leader of a dictatorship. Instead of occupying the highest leadership position himself until his death, Deng has let his “successor” assume office as the supreme leader while he is still alive and influential. Such an arrangement will help avoid a succession crisis and political upheavals upon Deng's death. In addition, the current market‐oriented economic reforms are very unlikely to be reversed in post‐Deng's China because of four factors: (1) public support of the reforms; (2) the vested interest of the “prince party” in the reforms; (3) the new leadership's commitment to the reforms; and (4) the constitutionalization of the reforms. However, there are three major sources of social unrest, which may lead to some political turbulence in the post‐Deng period. These sources are the “June 4th Incident” of 1989, public demand for an end of corruption and for political liberalization, and some socio‐economic problems...
Developmental exposure to endocrine-disrupting chemicals programs for reproductive tract alterations and obesity later in life

Many chemicals in the environment, especially those with estrogenic activity, are able to disrupt the programming of endocrine signaling pathways established during development; these chemicals are referred to as endocrine-disrupting chemicals. Altered programming can result in numerous adverse consequences in estrogen-target tissues, some of which may not be apparent until later in life. For example, a wide variety of structural, functional, and cellular effects have been identified in reproductive tract tissues. In addition to well-documented reproductive changes, obesity and diabetes have joined the list of adverse effects that have been associated with developmental exposure to environmental estrogens and other endocrine-disrupting chemicals. Obesity is a significant public health problem reaching epidemic proportions worldwide. Experimental animal studies document an association of developmental exposure to environmental estrogens and obesity. For example, a murine model of perinatal exposure to diethylstilbestrol has proven useful in studying mechanisms involved in abnormal programming of differentiating estrogen-target tissues, including reproductive tract tissues and adipocytes. Other environmental estrogens, including the environmental contaminant bisphenol A, have also been linked to reproductive problems and obesity later in life. Epidemiology studies support similar findings in humans, as do studies of cells in culture. Together, these findings suggest new targets for abnormal programming by estrogenic chemicals and provide evidence supporting the scientific concept termed the developmental origins of adult disease. Furthermore, the association of environmental estrogens with obesity and diabetes expands the focus on these diseases from intervention or treatment to include prevention or avoidance of chemical modifiers, especially during critical windows of development.
Evaluating With Sense The Theory-Driven Approach

Arguing for more serious theorizing in connection with evaluation, this article shows that although the randomized controlled experiment conceptualized as a "black box" approach has dominated the d...
Glomerular Cytochrome P-450 and Cyclooxygenase Metabolites Regulate Efferent Arteriole Resistance

Bradykinin dilates efferent arterioles via release of efferent arteriole epoxyeicosatrienoic acids when perfused retrograde (no glomerular autacoids). However, when efferent arterioles are perfused orthograde through the glomerulus, bradykinin-induced dilatation is caused by a balance between: (1) the glomerular vasoconstrictor 20-hydroxyeicosatetraenoic acid and vasodilator prostaglandins, and (2) epoxyeicosatrienoic acids from the efferent arteriole and possibly the glomerulus. However, the role of 20-hydroxyeicosatetraenoic acid has only been studied with a cyclooxygenase inhibitor, which may artificially enhance its production by shunting arachidonic acid into the cytochrome P450 pathway. We hypothesized that in the absence of cyclooxygenase inhibition, bradykinin induces release of 20-hydroxyeicosatetraenoic acid from the glomerulus, which blunts the vasodilator effect of bradykinin; and that prostaglandins released from glomeruli in response to bradykinin are generated by cyclooxygenase-1. Rabbit efferent arterioles preconstricted with norepinephrine were perfused orthograde from the end of the afferent arteriole. Bradykinin was added to the perfusate with or without a 20-hydroxyeicosatetraenoic acid antagonist (20-HEDE), epoxyeicosatrienoic acid synthesis inhibitor (MS-PPOH), and/or cyclooxygenase-1 (SC-58560) or cyclooxygenase-2 inhibitor (NS-398). Bradykinin-dependent dilatation was enhanced by 20-HEDE but blunted by MS-PPOH. When the inhibitors were present, bradykinin-induced dilatation was abolished by blockade of cyclooxygenase-1 but not cyclooxygenase-2. We concluded that: (1) in the absence of cyclooxygenase inhibitors, bradykinin causes the release of a glomerular vasoconstrictor (20-hydroxyeicosatetraenoic acid) that antagonizes the vasodilator effect of epoxyeicosatrienoic acids released from the efferent arteriole and perhaps from the glomerulus, and (2) bradykinin-induced vasodilatation is caused by the release of epoxyeicosatrienoic acids from the efferent arteriole and glomerular metabolites of cyclooxygenase-1.
Weight and Height Deficits in Children with Brain Stem Tumors

Weight deficit is common among children with brain stem tumors and is often accompanied by height deficit. Among 22 consecutive children (≤18 years) with brain stem tumor, 16 had weight deficit (≤20th percentile) (p<1.4e-7). Eleven were at or less than the 5th percentile, and 5 were less than the 1st weight percentile. Eight also had height deficit (≤20th percentile) (p<0.06). Misdiagnoses occurred: failure to thrive in 5, growth retardation in 2, and anorexia nervosa in 2. Delay between these diagnoses and that of brain tumor averaged 4.5 years. Detailed neuroradiologic study seems worthwhile if weight deficit is extreme and either unexplained or uncorrectable, or if the weight deficit is accompanied by an abnormality suggestive of intracranial disease.
Inherent Conflicts Of Interest In The Accounting Profession

In this paper, we critically examine three situations in the accounting/auditing profession in which conflicts of interest arise. Specifically, we describe conflicts of interest that occur (1) because audit fees are paid by the very companies being audited, (2) due to the tension built into accountants’ codes of professional ethics between the responsibility to maintain client confidentiality and the need to serve the public trust, and (3) because of most auditors’ perspective of who is their primary client. Based on our analysis, we conclude that these three inherent conflicts of interest, in the absence of some unforeseen revolutionary changes, are likely to persist within the auditing profession. We also conclude that attempts to mitigate some of these conflicts of interest through the Sarbanes-Oxley legislation have only been moderately successful. We therefore propose that audit professionals must learn to identify and manage the conflicts of interest that will likely remain a part of the profession for the indefinite future.
Decreasing Educational Segregation in Urban Schools to Reduce Risks Associated with Poverty: Current Reform Needs

Abstract This paper focuses on the problem of educational segregation within schools and shows how the continued use of categorical, “pull-out” programs exacerbates risks associated with poverty. It is suggested that educational segregation, as it disproportionately affects minority and poor children, is perhaps the civil rights issue facing the United States today due to increased diversity and worsening poverty in the inner cities. A strategy for systemic reform in schools is presented which is connected to the context of community as well as to efforts for long-term structural change. Reform recommendations are introduced that are linked to suggestions for collaborative political work and community organizing which could be used to effectively impact educational equity issues related to both segregation and poverty. Last, prospects for change during the remainder of the decade are analyzed with attention being directed toward the political mood of the mid-1990s and continued economic decline. It is sug...
The Ising Model

In this prototype theory of ferromagnetism—and of many other physical phenomena as well—a spin Si =±1 is assigned to each of N sites on a fixed lattice. The spins, which live on the vertices of the lattice, interact with one another by means of bonds (the links of the lattice). These have strengths Jij in energy units. In addition, the spins can interact with external fields Bi of arbitrary strengths. The total energy is then given by: $$H = - \sum {{J_{ij}}} {S_i}{S_j} - \sum {{B_i}} {S_i}$$ and can be directly evaluated in any of the 2N spin configurations. In the most familiar version of the Ising model, the interactions are limited to nearest-neighbors on the lattice and the magnetic field is homogeneous, Bi =constant.
Evaluating the Flexibility of the Java Sandbox

The ubiquitously-installed Java Runtime Environment (JRE) provides a complex, flexible set of mechanisms that support the execution of untrusted code inside a secure sandbox. However, many recent exploits have successfully escaped the sandbox, allowing attackers to infect numerous Java hosts. We hypothesize that the Java security model affords developers more flexibility than they need or use in practice, and thus its complexity compromises security without improving practical functionality. We describe an empirical study of the ways benign open-source Java applications use and interact with the Java security manager. We found that developers regularly misunderstand or misuse Java security mechanisms, that benign programs do not use all of the vast flexibility afforded by the Java security model, and that there are clear differences between the ways benign and exploit programs interact with the security manager. We validate these results by deriving two restrictions on application behavior that restrict (1) security manager modifications and (2) privilege escalation. We demonstrate that enforcing these rules at runtime stop a representative proportion of modern Java 7 exploits without breaking backwards compatibility with benign applications. These practical rules should be enforced in the JRE to fortify the Java sandbox.
On the Taylor Spectrum of M -Tuples of Analytic Toeplitz Operators on the Polydisk

We show that if \(F = (f_{1},\ldots,f_{m})\), where f i is in \(H^{\infty }(D^{n})\) and if \(T_{f_{i}}\) denotes the analytic Toeplitz operator acting on \(\mathcal{H} = H^{p}(D^{n})\) for 1 < p < ∞, then $$\displaystyle{\sigma _{T}((T_{f_{1}},\ldots,T_{f_{m}}),\mathcal{H}) = \overline{\text{ran}\,F(D^{n})}^{\mathbb{C}^{m} }.}$$ Here σ T denotes the Taylor spectrum.
The pathogenesis of narcolepsy, current treatments and prospective therapeutic targets

Introduction: Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness (EDS), cataplexy and abnormal manifestations of rapid eye movement (REM) sleep such as sleep paralysis and hypnagogic hallucinations. Recent studies have demonstrated that narcolepsy–cataplexy is caused by the postnatal loss of hypocretin neurons (Type 1 narcolepsy), possibly because of autoimmune mechanisms. Although several new therapeutic options have recently been introduced, these new findings have not yet been incorporated to the therapies.Areas covered: In this review, we first describe clinical symptoms and pathogenesis of narcolepsy. Second, we summarize the current knowledge about pharmacological treatments of narcolepsy and the modes of action of each drug. Finally, we discuss prospective therapeutic targets for narcolepsy.Expert opinion: Current treatments are mostly symptomatic, but it is necessary to initiate the appropriate pharmacological treatment for each symptom with the understanding of p...
Simultaneous indirect activity measurements of GH and PRL genes in the same, living mammosomatotrope

Dynamic intracellular processes in endocrine cells are usually controlled by the coordinated modulation of two or more functionally related genes. Attempts to gain a more complete understanding of these processes would be facilitated greatly by a method enabling activity measurements of two genes at the same time. Here we describe how we developed such a system and used it to determine indirectly whether individual, living pituitary cells could concurrently express both the growth hormone (GH) and prolactin (PRL) genes. Our results demonstrate that coexpression of these genes is indeed possible. Moreover, our findings provide a general paradigm for future “real-time” analysis of other interrelated genes involved in the regulation of endocrine processes.
Karl Lieblich: ein deutsch-jüdisches und schriftstellerisches Emigrantenschicksal zwischen Deutschland und Brasilien

Karl Lieblich’s story is one of a largely forgotten, German-Jewish writer who left Nazi Germany for exile in Brazil, later returning to Germany after the war. This articles reconstructs his life, analyzes his literary, cultural and philosophical writing and places it in its epoch.
Two-dimensional simulation of red blood cell motion near a wall under a lateral force.

The motion of a red blood cell suspended in a linear shear flow adjacent to a fixed boundary subject to an applied lateral force directed toward the boundary is simulated. A two-dimensional model is used that represents the viscous and elastic properties of normal red blood cells. Shear rates in the range of 100 to 600 ${\mathrm{s}}^{\ensuremath{-}1}$ are considered, and the suspending medium viscosity is 1 cP. In the absence of a lateral force, the cell executes a tumbling motion. With increasing lateral force, a transition from tumbling to tank-treading is predicted. The minimum force required to ensure tank-treading increases nonlinearly with the shear rate. Transient swinging motions occur when the force is slightly larger than the transition value. The applied lateral force is balanced by a hydrodynamic lift force resulting from the positive orientation of the long axis of the cell with respect to the wall. In the case of cyclic tumbling motions, the orientation angle takes positive values through most of the cycle, resulting in lift generation. These results are used to predict the motion of a cell close to the outer edge of the cell-rich core region that is generated when blood flows in a narrow tube. In this case, the lateral force is generated by shear-induced dispersion, resulting from cell-cell interactions in a region with a concentration gradient. This force is estimated using previous data on shear-induced dispersion. The cell is predicted to execute tank-treading motions at normal physiological hematocrit levels, with the possibility of tumbling at lower hematocrit levels.
Congenital rubella surveillance: a matter of priorities.

Congenital rubella syndrome (CRS) has been a nationally notifiable disease since 1965; however, reporting has been quantitatively poor. To improve surveillance, a National Registry for Congenital R...
Total Worker Health: A Promising Approach to a Safer and Healthier Workforce

Two articles present perspectives on the current science of the effectiveness of Total Worker Health interventions—employer-based interventions to promote health; disease management; control costs;...
Decreasing Prevalence of Chronic Kidney Disease in the United States: A Cause for Optimism

Murphy and colleagues analyze trends in the prevalence of CKD in U.S. adults. The editorialists note that, unfortunately, the observed improvement in prevalence has not been uniform across all popu...
Two Early Interactive Computer Network Experiments

Two early networking experiments joined a time-sharing computer at the System Development Corporation with systems at the Stanford Research Institute briefly in 1963 and at MIT Lincoln Laboratory in 1966-1967. Both were influenced by J.C.R. Licklider's interest in resource sharing and included experiments with the interactive use of remote programs.
Ga2O3 as Both Gate Dielectric and Surface Passivation via Sol-Gel Method at Room Ambient

We report the use of sol-gel method at room ambient to grow nanoscale thin film of Ga2O3 on Si surface for both surface passivation and gate dielectric. The admittance measurements were carried out in the frequency range of 20 kHz-1 MHz at room temperature. Voltage dependent profile of interfacial trap density (Dit) was obtained by using low and high frequency capacitance method. The capacitance (C)-voltage (V) analyses show that the structures have a low interfacial trap density (Dit) of 1x1012 cm-2eV-1. The Ga2O3 thin film synthesized via sol-gel method directly on devices to function as a gate dielectric film is found to be very effective. We also present our experimental results for a number of gate dielectric and device passivation applications.
Link, Writhe, and Twist

We review the concepts of writhe, twist, and linking as applied to space curves and ribbons. The application of these concepts to DNA is also discussed.
The Productivity Impact of Collaborative Research in the Economics of Risk and Uncertainty

A review of my research collaborations indicates that the principal motivations for coauthoring were the large scale of the project, the necessity of drawing on different economics skills, the involvement of researchers from other disciplines, and the training of graduate students. The summary statistics of my article collaborations indicate six coauthors of a dozen or more articles, but also a very large number of single collaborations. Overall, 167 of 331 articles and 9 of my 19 authored (not edited) books were singly authored, so coauthored work constitutes roughly half of my published output. Analysis of total articles published and coauthored articles by age indicates a life-cycle trajectory with coauthored work becoming increasingly prominent over time, with age 36 being the last year with no published coauthored work.
A Model for Behavioral Consultation in Rural School Districts

The demand for behavioral services is currently outpacing the availability of trained and certified behavior analysts. This need might be felt most acutely in rural communities, where educational funds often do not allow for hiring full-time behavioral staff. This article outlines a model for behavioral consultation that has been successful in several rural school districts. Strategies to build rapport, recommendations for assessment and treatment planning, and methods of expanding the role of the behavior analyst within the school are discussed. Finally, resources for teachers and administrative staff to access behavioral services and pertinent research are included.
Race, class, politics, and the disappearance of work: a rejoinder

I very much appreciate Jennifer Hochschild’s thoughtful commentary on my article, “When Work Disappears: New Implications for Race and Urban Poverty in the Global Economy” (1999). She focuses on tw...