cssi/SciSciGPT-SciSciNet huggingface dataset:
Electron Paramagnetic Resonance and Oxygen Binding Studies of α-Nitrosyl Hemoglobin A NOVEL OXYGEN CARRIER HAVING NO-ASSISTED ALLOSTERIC FUNCTIONS

alpha-Nitrosyl hemoglobin, alpha(Fe-NO)2beta(Fe)2, which is frequently observed upon reaction of deoxy hemoglobin with limited quantities of NO in vitro as well as in vivo, has been synthetically prepared, and its reaction with O2 has been investigation by EPR and thermodynamic equilibrium measurements. alpha-Nitrosyl hemoglobin is relatively stable under aerobic conditions and undergoes reversible O2 binding at the heme sites of its beta-subunits. Its O2 binding is coupled to the structural/functional transition between T- (low affinity extreme) and R- (high affinity) states. This transition is linked to the reversible cleavage of the heme Fe-proximal His bonds in the alpha(Fe-NO) subunits and is sensitive to allosteric effectors, such as protons, 2,3-biphosphoglycerate, and inositol hexaphosphate. In fact, alpha(Fe-NO)2beta(Fe)2 is exceptionally sensitive to protons, as it exhibits a highly enhanced Bohr effect. The total Bohr effect of alpha-nitrosyl hemoglobin is comparable to that of normal hemoglobin, despite the fact that the oxygenation process involves only two ligation steps. All of these structural and functional evidences have been further confirmed by examining the reactivity of the sulfhydryl group of the Cysbeta93 toward 4, 4'-dipyridyl disulfide of several alpha-nitrosyl hemoglobin derivatives over a wide pH range, as a probe for quaternary structure. Despite the halved O2-carrying capacity, alpha-nitrosyl hemoglobin is fully functional (cooperative and allosterically sensitive) and could represent a versatile low affinity O2 carrier with improved features that could deliver O2 to tissues effectively even after NO is sequestered at the heme sites of the alpha-subunits. It is concluded that the NO bound to the heme sites of the alpha-subunits of hemoglobin acts as a negative allosteric effector of Hb and thus might play a role in O2/CO2 transport in the blood under physiological conditions.
Novel heterojunction solar cells with conversion efficiencies approaching 21% on p-type crystalline silicon substrates

We report novel high-efficiency heterojunction (HJ) solar cells with Engineered Low-bandgap Interlayer and Thin Epitaxial emitter (ELITE) structure, achieving a record conversion efficiency of 20.7% on p-type crystalline Si (c-Si) substrates. Cell fabrication is based on plasma-enhanced chemical vapor deposition (PECVD) of contact layers at temperatures below 200°C and room-temperature sputtering of low-cost Al-doped zinc-oxide (ZnO:Al) electrodes.
Control of feeding behaviour and selective cannibalism in the rotifer Asplanchna

SUMMARY. Feeding responses in campanulate females of Asplanchna sieboldi were induced with filtrates of homogenized saccate female clonemates, showing that such behaviour can be triggered entirely by chemical stimuli. The failure of campanulates to attack campanulate clonemates, however, probably cannot be explained by the tissue chemistry of these females – filtered and unfiltered homogenates of campanulates were as active as those of saccates—and appears to be a function of some property limited to the campanulate body surface. The roles of chemical and physical properties of food items in controlling feeding behaviour in Asplanchna and other rotifers are considered.
A “Vaccination” of Willamette Spider Mites (Acari: Tetranychidae) to Prevent Large Populations of Pacific Spider Mites on Grapevines

Grape vineyards, Vitis vtnifera L., in the San Joaquin Valley that support populations of Willamette spider mites, Eotetranychus willamettei (McGregor), tend not to have outbreaks of Pacific spider mites, Tetranychus pacificus McGregor. Pacific spider mites are considered the more economically damaging of the mite species on grapes in this region. Earlier, small-scale experiments indicated strong negative interactions between these two species. We introduced Willamette spider mites into a commercial ‘Zinfandel’ vineyard that had a history of chronic problems with Pacific spider mites. In 1988, populations of Pacific spider mites were reduced significantly on rows to which we had released Willamette spider mites in fall 1987 compared with control rows. The effect was apparent throughout the growing season. The grower treated the vineyard with acaricide once in mid-summer and effectively reduced spider mite populations to undetectable levels. When populations of Pacific spider mites resurged in late summer, they were three times higher on control rows compared with rows to which we had previously released Willamette spider mites. When these rows were censused in 1989, we found no differences in mite populations between the two treatments. A second experiment releasing Willamette spider mites was done in 1989 in a different part of the same vineyard. At peak densities, Pacific spider mites were 3.5 times more numerous on control vines compared with vines that we had infested with Willamette spider mites earlier in the spring. In the first study in 1988, the two treatments did not differ in berry yield or sugar concentration measured at harvest. In 1989, yield for these vines also did not differ between treatments, but sugar concentration was higher for vines that we had inoculated with Willamette spider mites. In the second experiment, yields did not differ between treatments, but sugar concentrations were higher for vines that had received Willamette spider mites.
Tricorder: building a program analysis ecosystem

Static analysis tools help developers find bugs, improve code readability, and ensure consistent style across a project. However, these tools can be difficult to smoothly integrate with each other and into the developer workflow, particularly when scaling to large codebases. We present Tricorder, a program analysis platform aimed at building a data-driven ecosystem around program analysis. We present a set of guiding principles for our program analysis tools and a scalable architecture for an analysis platform implementing these principles. We include an empirical, in-situ evaluation of the tool as it is used by developers across Google that shows the usefulness and impact of the platform.
Health and economic benefits of bacterial vaccines in the prevention of otitis media

Evaluation of: O’Brien MA, Prosser LA, Paradise JL et al.: New vaccines against otitis media: projected benefits and cost-effectiveness. Pediatrics 123(6), 1452–1463 (2009). Vaccines have the potential to impact on otitis media, a leading cause of childhood morbidity. O ‘Brien et al. created a computerized model to project the potential health and economic benefits of bacterial vaccines targeted against Streptococcus pneumoniae, nontypeable Hemophilus influenzae and Moraxella catarrhalis against otitis media. They concluded that reasonably priced bacterial vaccines could achieve cost-effectiveness and potentially prevent millions of episodes of acute otitis media annually.
A V° importance function for the Monte Carlo calculation of the deep penetration of gamma rays

Abstract The successful application of the Monte Carlo method to problems involving the deep penetration of uncharged radiation requires the specification of an importance function which will identify and utilize those regions of phase space which contribute most heavily to the answer of interest. In the present work an importance function based on the first (or V) term of the series representation of the value (or adjoint) function is formulated and evaluated. For the case of 1 MeV gamma rays incident normally, on thick homogeneous slabs of lead and water, it was demonstrated that this V ° importance sampling scheme, which employs spatial, polar angle, and azimuthal biasing provides considerable improvement over the conventional exponential transform method. For the same computation times, the variance of the dose buildup factor at 21 in .f.p. was reduced by factors of about 125 and 50 for lead and water, respectively. For the particular source-geometry configuration investigated, it was determined that approximately equal reductions in variance was obtained by spatial and polar angle biasing with essentially no improvement provided by the azimuthal angle biasing.
The micro-politics of identity formation in the workplace: The case of a knowledge intensive firm*

This essay has been by necessity a gloss of a complex look at the relations of power, control, and personal identity construction in a workplace. Features of the nature of the work process combine with social strategies to construct a reproductive self-referential system. Corporate organizations are central institutions in contemporary life; they make developmental decisions for individuals and for society as a whole. While they are in this sense political to the core, we have not done enough to understand how this politics works or to explore its relation to people in a democratic society. Using a phenomenologically-based communication analysis enables a sensitive analysis of the multiple forms of power and domination as they exist in corporate sites. Although I have given only an outline of one case study here, this example suggests that phenomenologically-based projects can show harmful and unwarranted control, and can be a first step to fostering corporate practices that lead to decisions which are less wasteful of resources and more fully accomplish the goals of democratic society.
State-trace analysis: A method of testing simple theories of causation

Abstract An independent variable measures some aspect of a treatment applied to a person; a dependent variable measures some aspect of the treatment's effect upon the person. Two dependent variables will often covary with each other because they are affected by a common independent variable. A state trace is a graph which plots the value of one dependent variable as a function of another. (Thus, a state trace is a generalization of the yes-no receiver-operating-characteristic curve.) By appropriately analyzing state traces, it is possible to test theories concerning (a) the mechanisms by which independent variables affect dependent variables and (b) how these mechanisms differ from one population of persons to another. As an illustration, a study of long-term memory in normal persons, schizophrenics, and persons with organic brain syndrome is presented. The effects of number of word presentations and length of retention interval upon probability of word recall and recognition were investigated. The results were analyzed by state-trace analysis.
Light scattering and light transmittance of cadaver eye-explanted intraocular lenses of different materials.

Purpose To evaluate light scattering and light transmittance in cadaver eye–explanted intraocular lenses (IOLs) manufactured from different materials. Setting John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Design Experimental study. Methods Forty-nine pseudophakic cadaver eyes were selected according to IOL material/type and implantation duration, and the IOLs were explanted. Hydrophobic acrylic, hydrophilic acrylic, poly(methyl methacrylate) (PMMA), and silicone IOLs were included. Gross and light microscopy was performed for all IOLs. Light scattering was measured with an EAS 1000 Scheimpflug camera, and light transmittance was assessed using a Lambda 35 UV/Vis spectrophotometer (single-beam configuration with an RSA PE-20 integrating sphere). Analyses were performed at room temperature in the hydrated state and compared with analyses of controls. Results The highest levels of surface light scattering were measured for 3-piece hydrophobic acrylic, which was also the IOL type with the longest implantation duration among the Acrysof hydrophobic acrylic IOLs. Hydrophilic acrylic, PMMA, and silicone IOLs exhibited relatively low light-scattering levels. The lowest light-scattering levels were observed with PMMA IOLs (1-piece looped and 3-piece) and plate silicone IOLs, which represent the IOL types with the longest implantation duration in this series. Light transmittance values measured for all IOL types appeared to be similar to the values of the corresponding control IOLs. Conclusions The phenomenon of surface light scattering (nanoglistenings) is more particularly related to hydrophobic acrylic IOLs and increases with implantation time. No significant effect of surface light scattering on IOL light transmittance was found. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.
The Topodynamics of Incision of UV-irradiated Covalently Closed DNA by the Escherichia coli Uvr(A)BC Endonuclease

The Escherichia coli Uvr(A)BC endonuclease (Uvr(A)BC) initiates nucleotide excision repair of a large variety of DNA damages. The damage recognition and incision steps by the Uvr(A)BC is a complex process utilizing an ATP-dependent DNA helix-tracking activity associated with the UvrA2B1 complex. The latter activity leads to the generation of highly positively supercoiled DNA in the presence of E. coli topoisomerase I in vitro. Such highly positively supercoiled DNA, containing ultraviolet irradiation-induced photoproducts (uvDNA), is resistant to the incision by Uvr(A)BC, whereas the negatively supercoiled and relaxed forms of the uvDNA are effectively incised. The E. coli gyrase can contribute to the above reaction by abolishing the accumulation of highly positively supercoiled uvDNA thereby restoring Uvr(A)BC-catalyzed incision. Eukaryotic (calf thymus) topoisomerase I is able to substitute for gyrase in restoring this Uvr(A)BC-mediated incision reaction. The inability of Uvr(A)BC to incise highly positively supercoiled uvDNA results from the failure of the formation of UvrAB-dependent obligatory intermediates associated with the DNA conformational change. In contrast to Uvr(A)BC, the Micrococcus luteus UV endonuclease efficiently incises uvDNA regardless of its topological state. The in vitro topodynamic system proposed in this study may provide a simple model for studying a topological aspect of nucleotide excision repair and its interaction with other DNA topology-related processes in E. coli.
Medication Errors Versus Time of Admission in a Subpopulation of Stroke Patients Undergoing Inpatient Rehabilitation: Complications and Considerations

Purpose: This study looked at the medication ordering error frequency and the length of inpatient hospital stay in a subpopulation of stroke patients (n=60) as a function of time of patient admission to an inpatient rehabilitation hospital service. Method: A total of 60 inpatient rehabilitation patients, 30 arriving before 4 PM, and 30 arriving after 4 PM, with an admitting diagnosis of stroke were randomly selected from a larger sample (N=426). Results: There was a statistically significant increase in medication ordering errors and the number of inpatient rehabilitation hospital days in the group of patients who arrived after 4 PM.
Psychopharmacologic Investigations in Elderly Volunteers: Effect of Diazepam in Males†

Forty male volunteers over the age of 60 took either a daily dose of diazepam (12 mg) or placebo for a two-week period. Differential responses to these compounds partially depended upon age and the initial symptom level. Diazepam produced sedative side effects, a modest antidepressant effect, and a reduction in memory. Placebo had an antianxiety effect in the relatively older subjects, and was associated with decreased fatique, improved memory and improved motor function. Considerable variability was observed in both drug and placebo responses among the elderly. A self-rating depression scale (D30R) was useful for assessing changes in affective states and in discriminating between the effects of active drug and placebo.
A Life Course Perspective: Understanding Food Choices in Time, Social Location, and History

A life course perspective provides a framework for understanding how food choices develop in changing temporal, social, and historical contexts. This article describes the application of life course concepts to food choices, including trajectories, transitions, turning points, lives in place and time, and timing of events in lives. A life course approach to food choice can contribute to understanding the social and biological pathways of health risk and resilience over the life span. Life course analysis is a useful research and practice tool because of the many ways in which foods, the individuals choosing them, and food choice environments are changing.
Gynecologic pathology in the Macaca mulatta

Abstract A review of gynecologic pathology in the Macaca mulatta (rhesus) monkey reveals a glaring lack of information in this popular laboratory species. Accordingly, the reproductive tracts of a large group of females were examined to provide information on the type and prevalence of gynecologic pathology. A wide spectrum of pathologic findings were observed, most notably adenomyosis, ovarian cysts, subacute vaginitis, uterine vascular obliterative fibrosis, subacute and chronic inflammation of squamocolumnar junction, endometrial polyps, cervical dysplasia, and leiomyomas. One case of cervical carcinoma in situ was encountered.
Joint spacing and distribution in deformation band shear zones

Tectonic joints localized within deformation band shear zones on the Kaibab uplift in Utah, USA, show the same spacing and distribution characteristics as joints controlled by primary lithological mechanical stratigraphy, despite the fact that deformation band shear zones are secondary structural features oblique to primary sedimentary layers. The spacing and distribution of joints that traverse deformation band shear zones are important factors in the permeability and connectivity of sandstone reservoirs compartmentalized by deformation band shear zones.
Modeling system calls for intrusion detection with dynamic window sizes

We extend prior research on system call anomaly detection modeling methods for intrusion detection by incorporating dynamic window sizes. The window size is the length of the subsequence of a system call trace which is used as the basic unit for modeling program or process behavior. In this work we incorporate dynamic window sizes and show marked improvements in anomaly detection. We present two methods for estimating the optimal window size based on the available training data. The first method is an entropy modeling method which determines the optimal single window size for the data. The second method is a probability modeling method that takes into account context dependent window sizes. A context dependent window size model is motivated by the way that system calls are generated by processes. Sparse Markov transducers (SMTs) are used to compute the context dependent window size model. We show over actual system call traces that the entropy modeling methods lead to the optimal single window size. We also show that context dependent window sizes outperform traditional system call modeling methods.
Monoclonal Antibody Designated T2G1 Reacts With Human Fibrin β-Chain but Not With the Corresponding Chain From Mouse Fibrin

To the Editor: This communication concerns data presented by Tabrizi and coworkers,1 wherein the authors used antibody T2G1 to recognize mouse fibrin β-chain. There is some confusion as to the antibody, since the authors link T2G1 to a different antibody (designated 59D8) used in a separate study.2 Antibody T2G1 was prepared by our group,3 and to the best of our knowledge, no one has ever shown it to be reactive with mouse fibrin. At about the time we identified T2G1, Hui and coworkers4 described several antibodies, including 59D8, that reacted with human fibrin. To evaluate such monoclonals as clot imaging agents, we compared T2G1 and 59D8 and found that both were specific for the new NH2-terminus of fibrin β-chain.5 Matsueda and Margolies6 found that 59D8 also bound dog but not bovine, ovine, or porcine fibrins and speculated that Leu5 in the fibrin β-chain was the structural determinant underlying species specificity. A more recent study showed that antibody 59D8 also reacts with mouse fibrin β-chain.2 In contrast, we had observed that plastic-coated human3 as well as dog and rhesus monkey fibrinogen—after in situ activation with thrombin—bound T2G1, whereas mouse fibrinogen, treated in the same fashion, did not (B.J.K. et al, unpublished data, 1993). The results of Weiler-Guettler and coworkers2 prompted us to reexamine the reactivity of antibody T2G1 with mouse fibrin. The Figure⇓ shows that T2G1 reacts not only with fibrin β-chain made from pure human fibrinogen or clotted plasma but also with several …
Laser linewidth narrowing using transient spectral hole burning

Abstract We demonstrate significant narrowing of laser linewidths by high optical density materials with inhomogeneously broadened absorption. As a laser propagates through the material, the nonlinear spectral hole burning process causes a progressive self-filtering of the laser spectrum, potentially reaching values less than the homogeneous linewidth. The transient spectral hole dynamically adjusts itself to the instantaneous frequency of the laser, passively suppressing laser phase noise and side modes over the entire material absorption bandwidth without the need for electronic or optical feedback to the laser. Wide bandwidth laser phase noise suppression was demonstrated using Er3+ doped Y2SiO5 and LiNbO3 at 1.5 μm by employing time-delayed self-heterodyne detection of an external cavity diode laser to study the spectral narrowing effect. Our method is not restricted to any particular wavelength or laser system and is attractive for a range of applications where ultra-low phase noise sources are required.
Prescription Stimulant Expectancies in Recreational and Medical Users: Results from a Preliminary Expectancy Questionnaire

Given the rise of prescription stimulant misuse, examination of effect expectancies could prove helpful. The Prescription Stimulant Expectancy Questionnaire (PSEQ) was designed to explore positive and negative prescription stimulant-related expectancies. In 2006, 157 participants nationwide completed an Internet survey of prescription stimulant use, attention-deficit/hyperactivity disorder symptoms, and expectancies. Multiple regressions demonstrate that positive, but not negative expectancies, predicted frequency of use. Recreational and medical users were classified by hierarchical cluster analysis. Recreational users reported fewer positive and negative expectancies than medical users. Implications and limitations are discussed. Future research is warranted on prescription stimulant expectancies and the utility of the PSEQ.
Primary Care Providers Perceptions of Racial/Ethnic and Socioeconomic Disparities in Hypertension Control

Objective To evaluate the attitudes and perceptions of primary care providers (PCPs) regarding the presence and underlying sources of racial/ethnic and socioeconomic disparities in hypertension control. Methods We conducted a survey of 115 PCPs from 2 large academic centers in Colorado. We included physicians, nurse practitioners, and physician assistants. The survey assessed provider recognition and perceived contributors of disparities in hypertension control. Results Respondents were primarily female (66%), non-Hispanic White (84%), and physicians (80%). Among respondents, 67% and 73% supported the collection of data on the patients' race/ethnicity and socioeconomic status (SES), respectively. Eighty-six percent and 89% agreed that disparities in race/ethnicity and SES existed in hypertension care within the US health system. However, only 33% and 44% thought racial/ethnic and socioeconomic disparities existed in the care of their own patients. Providers were more likely to perceive patient factors rather than provider or health system factors as mediators of disparities. However, most supported interventions such as improving provider communication skills (87%) and cultural competency training (89%) to reduce disparities in hypertension control. Conclusions Most providers acknowledged that racial/ethnic and socioeconomic disparities in hypertension control exist in the US health system, but only a minority reported disparities in care among patients they personally treat. Our study highlights the need for testing an intervention aimed at increasing provider awareness of disparities within the local health setting to improve hypertension control for minority patients.
Plant biodiversity enhances bees and other insect pollinators in agroecosystems. A review

Thirty-five percent of global production from crops including at least 800 cultivated plants depend on animal pollination. The transformation of agriculture in the past half-century has triggered a decline in bees and other insect pollinators. In North America, losses of bee colonies have accelerated since 2004, leaving the continent with fewer managed pollinators than at any time in the past 50 years. A number of factors linked to industrial modes of agriculture affect bee colonies and other pollinators around the world, ranging from habitat degradation due to monocultures with consequent declines in flowering plants and the use of damaging insecticides. Incentives should be offered to farmers to restore pollinator-friendly habitats, including flower provisioning within or around crop fields and elimination of use of insecticides by adopting agroecological production methods. Conventional farmers should be extremely cautious in the choice, timing, and application of insecticides and other chemicals. Here, we review the literature providing mounting evidence that the restoration of plant biodiversity within and around crop fields can improve habitat for domestic and wild bees as well as other insects and thus enhance pollination services in agroecosystems. Main findings are the following: (1) certain weed species within crop fields that provide food resources and refuge should be maintained at tolerable levels within crop fields to aid in the survival of viable populations of pollinators. (2) Careful manipulation strategies need to be defined in order to avoid weed competition with crops and interference with certain cultural practices. Economic thresholds of weed populations, as well as factors affecting crop–weed balance within a crop season, need to be defined for specific cropping systems. (3) More research is warranted to advance knowledge on identifying beneficial weed species and ways to sponsor them to attract pollinators while not reducing yields through interference. (4) In areas of intensive farming, field margins, field edges and paths, headlands, fence-lines, rights of way, and nearby uncultivated patches of land are important refuges for many pollinators. (5) Maintenance and restoration of hedgerows and other vegetation features at field borders is therefore essential for harboring pollinators. (6) Appropriate management of non-cropped areas to encourage wild pollinators may prove to be a cost-effective means of maximizing crop yield.
A Surrogate Model based Constrained Optimization Architecture for the Optimal Design of Electrohydrostatic Actuators for Aircraft Flight Control Surfaces

This work pertains to the development of an optimization architecture for the optimal design of electrohydrostatic actuators for aircraft flight control surfaces in the presence of subsystem and aircraft level design constraints. A Modeling and Simulation (M&S) environment, described in detail in a separate work, is used to simulate an aircraft mission and capture relevant and constraining flight conditions and load cases. The system behavior is represented by a surrogate model that allows for rapid and computationally inexpensive evaluation of the responses of interest. The surrogate model is used to perform constrained optimization, followed by a validation of the optimal result using the M&S environment. The optimal designs obtained for two United States Air Force combat aircraft are presented and discussed, but the methodology is equally valid for other aircraft and control surface configurations. An additional capability arising from this architecture is the ability to analyze the sensitivity of the design to each of the design parameters influencing it.
Evaluating imaging biomarkers for neurodegeneration in pre-symptomatic Huntington's disease using machine learning techniques

The development of MRI measures as biomarkers for neurodegenerative disease could prove extremely valuable for the assessment of neuroprotective therapies. Much current research is aimed at developing such biomarkers for use in people who are gene-positive for Huntington's disease yet exhibit few or no clinical symptoms of the disease (pre-HD). We acquired structural (T1), diffusion weighted and functional MRI (fMRI) data from 39 pre-HD volunteers and 25 age-matched controls. To determine whether it was possible to decode information about disease state from neuroimaging data, we applied multivariate pattern analysis techniques to several derived voxel-based and segmented region-based datasets. We found that different measures of structural, diffusion weighted, and functional MRI could successfully classify pre-HD and controls using support vector machines (SVM) and linear discriminant analysis (LDA) with up to 76% accuracy. The model producing the highest classification accuracy used LDA with a set of six volume measures from the basal ganglia. Furthermore, using support vector regression (SVR) and linear regression models, we were able to generate quantitative measures of disease progression that were significantly correlated with established measures of disease progression (estimated years to clinical onset, derived from age and genetic information) from several different neuroimaging measures. The best performing regression models used SVR with neuroimaging data from regions within the grey matter (caudate), white matter (corticospinal tract), and fMRI (insular cortex). These results highlight the utility of machine learning analyses in addition to conventional ones. We have shown that several neuroimaging measures contain multivariate patterns of information that are useful for the development of disease-state biomarkers for HD.
Volume rendering of multimodal images: application to MRI and PET imaging of the human brain

A procedure for combining and visualizing complementary structural and functional information from magnetic resonance imaging (MRI) and positron emission tomography (PET) is described. MR and PET images of the human brain were obtained and correlated to form three-dimensional volumes of image data. Volume rendering and solid-texturing concepts were combined to develop a new volume imaging technique for 'volume texture-mapping' brain glucose metabolism (from PET) onto brain anatomy (from MRI). The technique was used to produce sequences of three-dimensional views: these sequences were dynamically displayed in a 'cine-loop' to better visualize the three-dimensional relationship between brain structure and function. The techniques provide a means of presenting vast amounts of multidimensional data in a form that is easily understood, and the resulting images are essential to an understanding of the normal and pathologic states of the human brain. >
Smooth Muscle α-Actin Gene Requires Two E-Boxes for Proper Expression In Vivo and Is a Target of Class I Basic Helix-Loop-Helix Proteins

Changes in the differentiated state of smooth muscle cells (SMCs) play a key role in vascular diseases, yet the mechanisms controlling SMC differentiation are still largely undefined. We addressed the role of basic helix-loop-helix (bHLH) proteins in SMC differentiation by first determining the role of two E-box (CAnnTG) motifs, binding sites for bHLH proteins, in the transcriptional regulation of the SMC differentiation marker gene, smooth muscle alpha-actin (SM alpha-actin), in vivo. Mutation of one or both E-boxes significantly reduced the expression of a -2560- to 2784-bp SM alpha-actin promoter/LacZ reporter gene in vivo in transgenic mice. We then determined the potential role of class I bHLH proteins, E12, E47, HEB, and E2-2, in SM alpha-actin regulation. In cotransfection experiments, E12, HEB, and E2-2 activated the SM alpha-actin promoter. Activation by HEB and E2-2 was synergistic with serum response factor. Additionally, the dominant-negative/inhibitory HLH proteins, Id2, Id3, and Twist, inhibited both the E12 and serum response factor-induced activations of the SM alpha-actin promoter. Finally, we demonstrated that E2A proteins (E12/E47) specifically bound the E-box-containing region of the SM alpha-actin promoter in vivo in the context of intact chromatin in SMCs. Taken together, these results provide the first evidence of E-box-dependent regulation of a SMC differentiation marker gene in vivo in transgenic mice. Moreover, they demonstrate a potential role for class I bHLH factors and their inhibitors, Id and Twist, in SM alpha-actin regulation and suggest that these factors may play an important role in control of SMC differentiation and phenotypic modulation.
Maternal Heterozygous Familial Hypercholesterolemia and Its Consequences for Mother and Child

During a normal pregnancy serum lipids (total, low-density lipoprotein [LDL]-cholesterol and high-density lipoprotein cholesterol, and triglycerides) rise steadily1 and take months to fall postpartum.2 LDL-cholesterol can increase by ≈66% and triglycerides can rise 3-fold, and it has been suggested that elevated cholesterol during pregnancy may be associated with spontaneous preterm delivery.3 Article see p 1606 It is known that women with heterozygous familial hypercholesterolemia (FH) who become pregnant have very high levels of LDL-cholesterol early in pregnancy (260 mg/dL or 6.7 mmol/L) that rise to even higher levels near term (330 mg/dL or 8.6 mmol/L).4 These very high lipid levels raise the question of the potential risks of pregnancy to the mother and fetus. FH is caused by mutations in the low-density lipoprotein receptor. In this issue of Circulation , in a study linking the Medical Birth Registry of Norway (1967–2006) and the Medical Genetics Laboratory at Oslo University Hospital that has established the molecular diagnosis in 4400 patients, 2319 births of 1093 women were identified.5 The serum levels of cholesterol in the nonpregnant, nontreated FH women were 370 mg/dL (9.59 mmol/L). In this study, no maternal cardiovascular deaths were observed. In addition, the children of mothers with FH were no more likely than the general population to be born prematurely, have low birth weight, or have congenital malformations. Furthermore, even though the sample size was small, no congenital malformations were observed in the 19 pregnancies associated with the use of lipid-lowering drugs during pregnancy. Although this is a retrospective, registry-based study, the data likely reflect the birth outcomes of a representative cohort of childbearing FH …
Modeling yield throughout the DRAM product life cycle

This paper presents a modeling technique for predicting DRAM die-per-wafer yield throughout a product's fabrication life cycle. Using manufacturing yield data, it is shown that an accurate mature yield prediction for a wide range of product types can be made by modifying the standard Poisson yield model to account for defect clustering, minimum dimension, and process complexity. It is also shown that an invariable learning factor can be derived using a learning curve equation based on average fabrication cycle time. This derivation leads to an accurate yield forecast through time.
IgM Repertoire Biodiversity is Reduced in HIV-1 Infection and Systemic Lupus Erythematosus.

Background: HIV-1 infection or systemic lupus erythematosus [SLE] disrupt B cell homeostasis, reduce memory B cells, and impair function of IgG and IgM antibodies. Objective: To determine how disturbances in B cell populations producing polyclonal antibodies relate to the IgM repertoire, the IgM transcriptome in health and disease was explored at the complementarity determining region 3 [CDRH3] sequence population level. Methods: 454-deep pyrosequencing in combination with a novel analysis pipeline was applied to define populations of IGHM CDRH3 sequences based on absence or presence of somatic hypermutations [SHM] in peripheral blood B cells. Results: HIV or SLE subjects have reduced biodiversity within their IGHM transcriptome compared to healthy subjects, mainly due to a significant decrease in the number of unique combinations of alleles, although recombination machinery was intact. While major differences between sequences without or with SHM occurred among all groups, IGHD and IGHJ allele use, CDRH3 length distribution, or generation of SHM were similar among study cohorts. Antiretroviral therapy failed to normalize IGHM biodiversity in HIV-infected individuals. All subjects had a low frequency of allelic combinations within the IGHM repertoire similar to known broadly-neutralizing HIV-1 antibodies. Conclusions: Polyclonal expansion would decrease overall IgM biodiversity independent of other mechanisms for development of the B cell repertoire. Applying deep sequencing as a strategy to follow development of the IgM repertoire in health and disease provides a novel molecular assessment of multiple points along the B cell differentiation pathway that is highly sensitive for detecting perturbations within the repertoire at the population level.
Molecular basis of neural-specific gene expression

Our understanding of how eukaryotic genes are regulated has improved dramatically over the past decade. This knowledge has been acquired, in part, by exposing the molecular interactions that underlie tissue-specific gene expression, including the very early events involved in cell fate deter­ mination. for many tissues, such as the immune system, liver, muscle, and pancreas, DNA elements and their cognate transcription factors that mediate both tissue-specific and developmental regulation of particular genes have been identified. Identification of the DNA elements and tran­ scription factors responsible for expression in the nervous system has been less forthcoming. Thcre are, however, several compelling reasons to study neural-specific gene expression. First, the mammalian brain is a very heterogeneous and complex organ within which numerous closely related, but distinct, neurons exist in a fantastically elaborated mosaic of cells. This complexity provides an unusual challenge to the specificity of the genetic regulatory apparatus, and some distinct molecular mechanisms may have developed to cope with this complexity. Second, changes in gene expression presumably underlie some aspects of the plasticity of the nervous system, such as learning and memory (Black et al 1 987; Goelet et al 1986). These changes are of considerable general interest to neuroscientists, and progress in under-
A mathematical model of mixing and polymerization in a semibatch stirred-tank reactor

Effects of mixing on number- and weight-average degree of polymerization in free radical homopolymerization in solution in a semibatch stirred tank reactor have been modeled by use of the 'partially segregated feed' model of Villermaux and the lumped kinetic treatment of addition polymerization
Lagrangian Motion, Coherent Structures, and Lines of Persistent Material Strain

Lagrangian motion in geophysical fluids may be strongly influenced by coherent structures that support distinct regimes in a given flow. The problems of identifying and demarcating Lagrangian regime boundaries associated with dynamical coherent structures in a given velocity field can be studied using approaches originally developed in the context of the abstract geometric theory of ordinary differential equations. An essential insight is that when coherent structures exist in a flow, Lagrangian regime boundaries may often be indicated as material curves on which the Lagrangian-mean principal-axis strain is large. This insight is the foundation of many numerical techniques for identifying such features in complex observed or numerically simulated ocean flows. The basic theoretical ideas are illustrated with a simple, kinematic traveling-wave model. The corresponding numerical algorithms for identifying candidate Lagrangian regime boundaries and lines of principal Lagrangian strain (also called Lagrangian ...
Phenylhydrazine-induced anemia causes nitric-oxide-mediated upregulation of the angiogenic pathway in Notothenia coriiceps.

SUMMARY Antarctic icefishes possess several cardiovascular characteristics that enable them to deliver oxygen adequately in the absence of hemoglobin (Hb). To gain insight into mechanisms driving development of these cardiovascular characteristics of icefish, we chemically induced severe anemia in a red-blooded notothenioid, Notothenia coriiceps. After 10 days of treatment with phenylhydrazine HCl, the hematocrit and Hb concentration of N. coriiceps decreased by >90% and >70%, respectively. Anemic fish exhibited a significantly higher concentration of nitric oxide (NO) metabolites in their plasma compared with that of control animals, indicating that corporeal levels of NO are higher in anemic animals than in control fish. The activity of nitric oxide synthase (NOS) was measured in brain, retina, pectoral muscle and ventricle of control and anemic animals. With the exception of retina, no significant differences in NOS activities were observed, indicating that the increase in plasma NO metabolites is due to loss of Hb, which normally plays a major role in the degradation of NO, and not due to an overall increase in the capacity for NO production. To determine whether loss of Hb can stimulate remodeling of the cardiovascular system, we measured expression of HIF-1α, PHD2 and VEGF mRNA in retinae of control and anemic fish. Expression of all three genes was higher in anemic animals compared with control N. coriiceps, suggesting a causative relationship between loss of Hb and induction of angiogenesis that probably is mediated through nitric oxide signaling.
Attorneys' Questions and Children's Productivity in Child Sexual Abuse Criminal Trials

We investigated the links between questions child witnesses are asked in court, children's answers, and case outcome. Samples of acquittals and convictions were matched on child age, victim-defendant relationship, and allegation count and severity. Transcripts were coded for question types, including a previously under-examined type of potentially suggestive question, declarative questions. Children's productivity was conceptualized in a novel way by separating new from repeated content and by adjusting the definition based on the linguistic demands of the questions. Attorneys frequently used declarative questions, and disconcertingly, attorneys who used these and other suggestive questions more frequently were more likely to win their case. Open-ended and closed-ended questions elicited similar levels of productivity from children, and both elicited more productivity compared with suggestive questions. Results highlight how conceptualization of questions and answers can influence conclusions, and demonstrate the important real-world implications of attorney questioning strategies on legal cases with child witnesses.
Modeling and validating chronic pharmacological manipulation of circadian rhythms.

Circadian rhythms can be entrained by a light-dark (LD) cycle and can also be reset pharmacologically, for example, by the CK1δ/e inhibitor PF-670462. Here, we determine how these two independent signals affect circadian timekeeping from the molecular to the behavioral level. By developing a systems pharmacology model, we predict and experimentally validate that chronic CK1δ/e inhibition during the earlier hours of a LD cycle can produce a constant stable delay of rhythm. However, chronic dosing later during the day, or in the presence of longer light intervals, is not predicted to yield an entrained rhythm. We also propose a simple method based on phase response curves (PRCs) that predicts the effects of a LD cycle and chronic dosing of a circadian drug. This work indicates that dosing timing and environmental signals must be carefully considered for accurate pharmacological manipulation of circadian phase.
Comparison of Alveolar Bone Loss, Alveolar Bone Density and Second Metacarpal Bone Density, Salivary and Gingival Crevicular Fluid Interleukin-6 Concentrations in Healthy Premenopausal and Postmenopausal Women on Estrogen Therapy

Background. Osteoporosis is an age-related metabolic bone disease characterized by decreased mass and increased susceptibility to fracture. The literature suggests a relationship between oral bone loss and skeletal osteoporosis; however, most studies have produced conflicting results. The purpose of this study was to determine if a relationship exists among alveolar bone loss, alveolar bone density, second metacarpal density, salivary and gingival crevicular fluid interleukin 6 (IL-6), and IL-8 concentrations in premenopausal and postmenopausal healthy women receiving estrogen therapy. Methods. Twenty-eight healthy women (aged 23-78) were evaluated for this study. A vertical bitewing and hand radiographs were taken, and the subjects were evaluated for the presence of active periodontitis. The bitewing and hand radiographs were digitized, and measurements were made from the cemento-enamel junction to the alveolar crest from both arches. Bone density was evaluated in the maxillary and mandibular alveolar process and at the mid-shaft of the second metacarpal. Percent cortical area and the moment of inertia measurements were also determined. Stimulated whole saliva was collected for a 5-min period using a cube of paraffin as a stimulant and was analyzed for total protein by a colorimetric reaction and IL-6 and IL-8 by ELISA. Results. The results of the study showed that postmenopausal women on estrogen therapy had more alveolar bone loss, more missing teeth, and reduced alveolar and second metacarpal bone density than premenopausal women. In addition, postmenopausal women on estrogen therapy had higher salivary IL-6 concentrations than premenopausal women. Alveolar bone densities were also strongly correlated to second metacarpal densities. Conclusions. The results of the study suggest that changes in alveolar bone density and levels of bone resorptive cytokines in saliva may be secondary to changes in menopausal status. These changes may predispose loss of alveolar bone with resultant loss of teeth.
Photoreceptor transplantation in retinitis pigmentosa: short-term follow-up

Abstract Purpose To explore the use of adult human photoreceptor transplantation as a treatment for advanced retinitis pigmentosa (RP). Design Prospective noncomparative case series. Participants Eight patients with advanced RP. Intervention Transplantation of adult human cadaver photoreceptor sheets harvested with the excimer laser. No immunosuppression was used postoperatively. Patients were followed for 12 months postoperatively. Main outcome measure Visual acuity and retinal function measured by psychophysical, electrophysiologic, and clinical testing. Results Best-corrected visual acuity (Bailey-Lovie chart), median reading speed, contrast sensitivity, and visual fields for the operated eye were not statistically significantly improved postoperatively. The amplitude and latency of the maculoscope electroretinogram, as well as the log threshold for dark adaptation, did not change between the operated and control (unoperated) eye. There was no detectable homograft reaction on slit-lamp biomicroscopy or fluorescein angiography. The only adverse effect observed was one patient who complained of monocular diplopia after retinal transplantation and subsequent cataract surgery. Conclusions Allogeneic adult human photoreceptor transplantation is feasible in RP but was not associated with rescue of central vision or a delay in visual loss. However, any possible slowing in the rate of retinal degeneration will take many years to determine.