cssi/SciSciGPT-SciSciNet huggingface dataset:
Rapid in silico design of antibodies targeting SARS-CoV-2 using machine learning and supercomputing

Summary Rapidly responding to novel pathogens, such as SARS-CoV-2, represents an extremely challenging and complex endeavor. Numerous promising therapeutic and vaccine research efforts to mitigate the catastrophic effects of COVID-19 pandemic are underway, yet an efficacious countermeasure is still not available. To support these global research efforts, we have used a novel computational pipeline combining machine learning, bioinformatics, and supercomputing to predict antibody structures capable of targeting the SARS-CoV-2 receptor binding domain (RBD). In 22 days, using just the SARS-CoV-2 sequence and previously published neutralizing antibody structures for SARS-CoV-1, we generated 20 initial antibody sequences predicted to target the SARS-CoV-2 RBD. As a first step in this process, we predicted (and publicly released) structures of the SARS-CoV-2 spike protein using homology-based structural modeling. The predicted structures proved to be accurate within the targeted RBD region when compared to experimentally derived structures published weeks later. Next we used our in silico design platform to iteratively propose mutations to SARS-CoV-1 neutralizing antibodies (known not to bind SARS-Cov-2) to enable and optimize binding within the RBD of SARS-CoV-2. Starting from a calculated baseline free energy of −48.1 kcal/mol (± 8.3), our 20 selected first round antibody structures are predicted to have improved interaction with the SARS-CoV-2 RBD with free energies as low as −82.0 kcal/mole. The baseline SARS-CoV-1 antibody in complex with the SARS-CoV-1 RBD has a calculated interaction energy of −52.2 kcal/mole and neutralizes the virus by preventing it from binding and entering the human ACE2 receptor. These results suggest that our predicted antibody mutants may bind the SARS-CoV-2 RBD and potentially neutralize the virus. Additionally, our selected antibody mutants score well according to multiple antibody developability metrics. These antibody designs are being expressed and experimentally tested for binding to COVID-19 viral proteins, which will provide invaluable feedback to further improve the machine learning–driven designs. This technical report is a high-level description of that effort; the Supplementary Materials includes the homology-based structural models we developed and 178,856 in silico free energy calculations for 89,263 mutant antibodies derived from known SARS-CoV-1 neutralizing antibodies.
Multiscale modal analysis of fully-loaded spent nuclear fuel canisters

Abstract In this paper, an efficient numerical procedure is proposed, which is adapted to the modal analysis of a fully-loaded spent nuclear fuel canister exhibiting distinct structural levels associated with a hierarchy of components. On the one hand, the fully-loaded spent nuclear fuel canister is constituted of a repetition of identical components, resulting in a pseudo-periodicity; and the components of a given level are separated from each other and only connected to their upper level through localized attachments. This gives rise to an advantageous structural connectivity that can be exploited for efficiency. On the other hand, the necessary fine mesh resolution of the small levels leads to a high-dimensional computational model and, in addition, the independent resonant vibrations of each of the components produce a very large number of vibration eigenmodes. The aforementioned opportunities and difficulties are respectively leveraged and tackled by an adapted method that combines domain decomposition, shift–invert Lanczos eigenvalue solver, and Craig–Bampton substructuring technique. A parallel eigensolution via spectrum slicing is facilitated by an efficient block factorization by Schur complement due to the sparsity of the Craig–Bampton matrices. A computational gain of four orders of magnitude is obtained, at the expense of negligible errors that are exactly characterized. The proposed methodology enables a high-fidelity vibration analysis of the sealed fully-loaded spent nuclear fuel canister, useful for non-intrusive inverse identification of the structural integrity of the internal structural levels holding the nuclear material.
Improving VQA and its Explanations by Comparing Competing Explanations

Most recent state-of-the-art Visual Question Answering (VQA) systems are opaque black boxes that are only trained to fit the answer distribution given the question and visual content. As a result, these systems frequently take shortcuts, focusing on simple visual concepts or question priors. This phenomenon becomes more problematic as the questions become complex that requires more reasoning and commonsense knowledge. To address this issue, we present a novel framework that uses explanations for competing answers to help VQA systems select the correct answer. By training on human textual explanations, our framework builds better representations for the questions and visual content, and then reweights confidences in the answer candidates using either generated or retrieved explanations from the training set. We evaluate our framework on the VQA-X dataset, which has more difficult questions with human explanations, achieving new state-of-the-art results on both VQA and its explanations.
A Modular Multilevel Converter with Integrated Self-balancing Series IGBTs

Modular multilevel converters (MMC) and series-connected IGBTs are two promising solutions to high-voltage dc (HVDC) transmission. It has been shown that, when integrated with series IGBTs, a MMC can benefit from a reduced number of sub-modules (SMs), simpler control, and improved reliability. In this paper, a MMC prototype, with the capability to integrate series IGBTs to replace single IGBTs in the sub-modules, is designed and developed. The MMC control is realized with a real-time simulator for versatile software implementation. The voltage sharing among the series IGBTs is regulated locally without the intervention of the central control. Furthermore, voltage balance under bi-directional current through the series strings is achieved. Experiments were conducted where individual IGBTs in one sub-module were replaced with a series of three IGBTs each. The results verify that the MMC is functional since the local series IGBT control and the MMC central control are independent. It is also verified that both series strings can maintain voltage balance at the same time even though the string currents shift directions.
From Treasure to Trash: The Changing Meaning of Books in the New Social Economy of Higher Education:

This paper draws on the findings of an autoethnographic study to discuss significant changes in the character of US institutions of higher education in recent decades. The autoethnography incorpora...
High-quality graphene as a coating for polycrystalline tungsten in low-energy helium and deuterium plasma exposures

Abstract In the presence of irradiation by energetic ions, plasma facing components (PFCs) tend to develop surface morphologies that lead to mass loss of the wall material, potentially diminishing their lifetime and plasma performance. We explore the performance of graphene as a coating for plasma facing components to protect against sputtering due to low-energy ions. We show that graphene can slow changes in surface morphology of tungsten subjected to energetic-helium and deuterium ion bombardment over a wide range of energies, as tested in the PISCES-A facility at UC-San Diego. We exposed tungsten samples half-coated with graphene in the PISCES-A facility, at energies of 40 and 140 eV and fluences ranging from 1 × 1024 - 3.6 × 1025 ions/m2. We found that tungsten “fuzz” growth at high fluences (1024–1025 He-D/m2) can be reduced by approximately 30%. At the lower fluence and energy, no fuzz formed. Using scanning electron microscopy and focused-ion beam machining, we investigate these changes in surface morphology. Deuterium results do not show the graphene defect production to be as energy or fluence dependent as helium bombardment. We determine damage to and the lifetime of the graphene membrane with Raman spectroscopy for vacuum components subjected to such extreme environmental conditions.
ALD-passivated silicon nanowires for broadband absorption applications

Silicon photonics enables the fabrication of optical devices with standard semiconductor processing technology. With high transparency and modal confinement, Si has matured into a well-established infrared optical material. Nanostructured silicon has been studied extensively due to its optical properties, especially silicon nanowires due to the myriad of available fabrication techniques, the broad range of physical dimensions, and the resulting optical characteristics. In this study, we fabricate silicon nanowires using a wet chemical process and modify their absorptive properties via atomic layer deposition passivation. The passivated nanowires absorb 95% of light from the visible to infrared, with a minimal angular dependence, making them excellent candidates for broadband absorber applications.
Parker winds revisited: an extension to disc winds

A simple 1D dynamical model of thermally driven disc winds is proposed, based on the results of recent, 2.5D axisymmetric simulations. Our formulation of the disc wind problem is in the spirit of the original Parker and Bondi problems, namely we assume an elementary flow configuration consisting of an outflow following pre-defined trajectories in the presence of a central gravitating point mass. Viscosity and heat conduction are neglected. We consider two different streamline geometries, both comprised of straight lines in the (x, z)-plane: (i) streamlines that converge to a geometric point located at (x, z) = (0, −d) and (ii) streamlines that emerge at a constant inclination angle from the disc mid-plane (the x-axis, as we consider geometrically thin accretion discs). The former geometry is commonly used in kinematic models to compute synthetic spectra, while the latter, which exhibits self-similarity, is likely unused for this purpose, although it easily can be with existing kinematic models. We make the case that it should be, i.e. geometry (ii) leads to transonic wind solutions with substantially different properties owing to its lack of streamline divergence. Both geometries can be used to complement recent efforts to estimate photoevaporative mass-loss rates from protoplanetary discs. Pertinent to understanding our disc wind results, which are also applicable to X-ray binaries and active galactic nuclei, is a focused discussion on lesser known properties of classic Parker wind solutions. We find that the parameter space corresponding to decelerating Parker wind solutions is made larger due to rotation and leads instead to disc wind solutions that always accelerate after the bulk velocity is slowed to a minimum value. Surprisingly, Keplerian rotation may allow for two different transonic wind solutions for the same physical conditions.
Quantifying Disaster Impacts on Local Public Health Agency's Leadership, Staffing, and Provision of Essential Public Health Services.

Objective The objective of this study is to assess the impact that natural disaster response has on local health departments' (LHD) ability to continue to provide essential public health services. Methods A web-based survey was sent to all North Carolina Local Health Directors. The survey asked respondents to report on LHD functioning following Hurricanes Florence (2018) and Dorian (2019). Results After Hurricane Florence, the positions who most frequently had regular duties postponed or interrupted were leadership (15 of 48; 31.3%), and professional staff (e.g., nursing and epidemiology: 11 of 48; 22.9%). Staffing shelters for all phases - from disaster response through long-term recovery - was identified as a burden by LHDs, particularly for nursing staff. Approximately 66.6% of LHD jurisdictions opened an Emergency Operations Center (EOC) or activated Incident Command System in response to both hurricanes. If an EOC was activated, the LHD was statistically, significantly more likely to report that normal duties had been interrupted across every domain assessed. Conclusions The ability of LHDs to perform regular activities and provide essential public health services is impacted by their obligations to support disaster response. Better metrics are needed to measure the impacts to estimate indirect public health impacts of disasters.
Machine Learning Can Assign Geologic Basin to Produced Water Samples Using Major Ion Geochemistry

Understanding the geochemistry of waters produced during petroleum extraction is essential to informing the best treatment and reuse options, which can potentially be optimized for a given geologic basin. Here, we used the US Geological Survey’s National Produced Waters Geochemical Database (PWGD) to determine if major ion chemistry could be used to classify accurately a produced water sample to a given geologic basin based on similarities to a given training dataset. Two datasets were derived from the PWGD: one with seven features but more samples (PWGD7), and another with nine features but fewer samples (PWGD9). The seven-feature dataset, prior to randomly generating a training and testing (i.e., validation) dataset, had 58,541 samples, 20 basins, and was classified based on total dissolved solids (TDS), bicarbonate (HCO3), Ca, Na, Cl, Mg, and sulfate (SO4). The nine-feature dataset, prior to randomly splitting into a training and testing (i.e., validation) dataset, contained 33,271 samples, 19 basins, and was classified based on TDS, HCO3, Ca, Na, Cl, Mg, SO4, pH, and specific gravity. Three supervised machine learning algorithms—Random Forest, k-Nearest Neighbors, and Naive Bayes—were used to develop multi-class classification models to predict a basin of origin for produced waters using major ion chemistry. After training, the models were tested on three different datasets: Validation7, Validation9, and one based on data absent from the PWGD. Prediction accuracies across the models ranged from 23.5 to 73.5% when tested on the two PWGD-based datasets. A model using the Random Forest algorithm predicted most accurately compared to all other models tested. The models generally predicted basin of origin more accurately on the PWGD7-based dataset than on the PWGD9-based dataset. An additional dataset, which contained data not in the PWGD, was used to test the most accurate model; results suggest that some basins may lack geochemical diversity or may not be well described, while others may be geochemically diverse or are well described. A compelling result of this work is that a produced water basin of origin can be determined using major ions alone and, therefore, deep basinal fluid compositions may not be as variable within a given basin as previously thought. Applications include predicting the geochemistry of produced fluid prior to drilling at different intervals and assigning historical produced water data to a producing basin.
Transitions in the Nervous System during Amphibian Metamorphosis

The tadpole as a whole can be considered to be an aggregate of mosaic territories, each responding in a distinctive way to the increased titers of thyroid hormones (TH) responsible for progressive metamorphic changes. Similarly, the separate elements of the nervous system can be considered, at least as a first approximation, to be composed of a series of mosaic territories. They differ as to the stages when they are first morphologically distinguishable, when they first acquire capacity to respond to TH, in the rates of increase in such sensitivity, i.e., in reduction of threshold concentrations required to elicit detectable change, and in the rates of response to given concentrations. They probably also differ with respect to the hormone concentrations required to elicit maximal rates of tissue response. Some elements of the nervous system grow and differentiate; others shrink, die, and disappear. The extent to which there may be elements of the nervous system that are unresponsive to TH remains largely to be established.
Studies in lead poisoning. I. Microanalysis of erythrocyte protoporphyrin levels by spectrophotometry in the detection of chronic lead intoxication in the subclinical range

Abstract This study describes the application of a rapid, simple, extremely sensitive new assay for blood protoporphyrin to the detection of lead poisoning in the subclinical range. This protoporphyrin method has proved to be especially useful for the detection of chronic lead intoxication in children because of its precision and the fact that only 2 μl of blood are required for the analysis. Blood protoporphyrin was found to reflect better the level of bone marrow lead existing 2–3 months prior to sampling rather than the circulating blood lead level. The correlation coefficient between log blood protoporphyrin and blood lead was found to be 0.72. Over 95% of the population with a blood lead level of 0.06 mg/100 ml had a protoporphyrin concentration of ≧ 140 μg/100 ml RBC. When a group of children was selected whose blood lead was in equilibrium with bone marrow lead, the correlation coefficient was 0.91. Several micromethods for the detection of lead poisoning are discussed; using a combination of this new protoporphyrin assay together with either the determination of blood lead, the presence of increased eythrocytic osmotic resistance or the measurement of δ-aminolevulinic acid dehydratase, permits a distinction to be made between acute and chronic lead poisoning and/or iron deficiency anemia.
Amino Acids, Peptides and Proteins

In this chapter we summarize the nomenclature and certain properties pertaining to proteins and their constituents. Additional information is readily available in standard works on biochemistry such as Fruton and Simmonds (1958), Edsall and Wyman (1958), Mahler and Cordes (1967), Dickerson and Geis (1969) and Lehninger (1970).
Limits of Exact Algorithms For Inference of Minimum Size Finite State Machines

We address the problem of selecting the minimum sized finite state machine consistent with given input/output samples. The problem can be solved by computing the minimum finite state machine equivalent to a finite state machine without loops obtained from the training set. We compare the performance of four algorithms for this task: two algorithms for incompletely specified finite state machine reduction, an algorithm based on a well known explicit search procedure and an algorithm based on a new implicit search procedure that is introduced in this paper.
Region based image segmentation using a modified Mumford-Shah algorithm

The goal of this paper is to develop region based image segmentation algorithms. Two new variational PDE image segmentation models are proposed. The first model is obtained by minimizing an energy function which depends on a modified Mumford-Shah algorithm. The second model is acquired by utilizing prior shape information and region intensity values. The numerical experiments of the proposed models are tested against synthetic data and simulated normal human-brain MR images. The preliminary experimental results show the effectiveness and robustness of presented models against to noise, artifact, and loss of information.
The Effects of Coordination Failure and Moral Hazard on the Efficiency of Cogsa's Package Limitation

Under Sec. 3(8) and 4(5) of the Carriage of Goods by Sea Act, liability is allocated to the common carrier for damages to cargo valued less than 500, and the carrier may not reallocate any of this liability to the cargo owner. The paper analyzes the economic effect of the regime, and shows that it induces a particular level of care, but also points to the package limitation's distortionary effects. A decentralized limitation is shown to be superior to COGSA's, but the presense of moral hazard and coordination failure prevent a solution that optimizes investments in precautions against cargo damages, thus minimizing insurance costs.
E.U. Condon — The Physicist and the Individual

Having heard Dr. Branscomb’s talk, I think we will turn the program around, as he gave Condon’s importance for physics, and I will talk more about Condon the individual, and the times in which he lived, and something about the scientific scene in the United States at that time and some of his influence on that and through that on the world.
Noise dependence of high bit-rate optical chaotic communication back-to-back systems

A comparative study of three data encoding techniques in optical chaotic communication systems is presented, for different RIN levels and bit-rates. High noise level deteriorates the decoded message quality, while after filtering its effect is minimized.
The Time to Most Recent Common Ancestor Does Not (Usually) Approximate the Date of Divergence

With the advent of more sophisticated models and increase in computational power, an ever-growing amount of information can be extracted from DNA sequence data. In particular, recent advances have allowed researchers to estimate the date of historical events for a group of interest including time to most recent common ancestor (TMRCA), dates of specific nodes in a phylogeny, and the date of divergence or speciation date. Here I use coalescent simulations and re-analyze an empirical dataset to illustrate the importance of taxon sampling, in particular, on correctly estimating such dates. I show that TMRCA of representatives of a single taxon is often not the same as divergence date due to issues such as incomplete lineage sorting. Of critical importance is when estimating divergence or speciation dates a representative from a different taxonomic lineage must be included in the analysis. Without considering these issues, studies may incorrectly estimate the times at which historical events occurred, which has profound impacts within both research and applied (e.g., those related to public health) settings.
Abstract P157: Serum Vitamin D is Not Associated With Risk of Incident Diabetes in African Americans: The Jackson Heart Study

A recent meta-analysis of cohort studies with participants primarily of European ancestry, concluded that the risk of incident diabetes was inversely proportional to serum 25-hydroxy-vitamin D levels (25-OH-D). African Americans have lower levels of vitamin D than European Americans. But, lower levels of vitamin D do not seem to carry the same risk for low bone density or vascular calcification for African Americans. We sought to test the hypothesis that low vitamin D elevates the risk of diabetes in African Americans. During 2001-5, 5301 African American adults in Jackson, MS, were examined and blood samples drawn; mean age was 55±13. Serum 25-OH-D2 and 25-OH-D3 were measured from stored frozen serum; mean total 25-OH-D (25-OH-D2 plus 25-OH-D3) =14.5±6.7ng/ml. A seasonal pattern was evident for 25-OH-D3 but not for 25-OH-D2 levels. A cosinor model adjusted for seasonality of 25-OH-D3; mean annualized concentrations and seasonal amplitude were significantly higher for men and for persons of normal BMI compared to overweight or obese persons. Total 25-OH-D, as the sum of predicted annualized mean 25-OH-D3 and measured 25-OH-D2, was used in subsequent analysis. The analysis evaluated 3363 participants after exclusions for missing serum vitamin D (n=141), prevalent diabetes (n=1152), incomplete ascertainment of diabetes (n=62), or no follow-up (n=725). During a mean follow-up of 7.1 years, there were 584 new cases of diabetes. Using a Cox Proportional Hazards model controlling for age and sex, the risk of incident diabetes was significantly and inversely associated with total serum 25-OH-D; after adding BMI to the model, 25-OH-D was not significantly associated with risk of diabetes (Table 1). Physical activity, smoking, and alcohol use did not predict incident diabetes in any model. In conclusion, we found that in this cohort of African-Americans, with low mean 25-OH-D and a relatively narrow range of 25-OH-D, the risk of incident diabetes was not associated with serum 25-OH-D levels after controlling for sex, age, and BMI.
Modeling of PGA lines considering electromagnetic coupling based on high frequency measurements

Electromagnetic coupling of pin-grid array (PGA) lines may cause problems in sensitive circuits. Models that are based upon measurements in a wide frequency range and which consider coupling effects are needed for the estimation of the electrical performance of a package. To enable high-frequency measurements of a four port device under test (DUT) with a two port network analyzer using microwave probes, a complex measurement setup including special contact structures is designed. The complete model of the DUT includes contact structures and lines on both the board, as well as on the chiplevel, the wirebond and pin grid array (PGA)-lines. The contact structures, lines and the wirebonds are modeled separately. >
Immune function is impaired in iron-deficient, homebound, older women.

Background Aging is often associated with a dysregulation of immune function. Iron deficiency may further impair immunity in older adults. Published reports on iron deficiency and immune response in humans are inconsistent. Most studies are focused on young children in developing countries and are often confounded by comorbid conditions, infections, and nutrient deficiencies. Objective Our objective was to determine the relation of iron status with immune function in homebound older women, who often have impairments in both iron status and immune response. The subjects were selected according to rigorous exclusion criteria for disease, infection, and deficiencies in key nutrients known to affect immunocompetence. Design Seventy-two homebound elderly women provided blood for comprehensive evaluation of iron status and cell-mediated and innate immunity. Women were classified as iron-deficient or iron-sufficient on the basis of multiple abnormal iron status test results. Groups were compared with respect to lymphocyte subsets, phagocytosis, oxidative burst capacity, and T cell proliferation upon stimulation with mitogens. Results In iron-deficient women, T cell proliferation upon stimulation with concanavalin A and phytohemagglutinin A was only 40-50% of that in iron-sufficient women. Phagocytosis did not differ significantly between the 2 groups, but respiratory burst was significantly less (by 28%) in iron-deficient women than in iron-sufficient women. Conclusions Iron deficiency is associated with impairments in cell-mediated and innate immunity and may render older adults more vulnerable to infections. Further prospective studies using similar exclusion criteria for disease, infection, and concomitant nutrient deficiencies are needed for simultaneous examination of the effects of iron deficiency on immune response and morbidity.
Failure of HIV-exposed CD4+ T cells to activate dendritic cells is reversed by restoration of CD40/CD154 interactions

Because interactions between activated CD4+ T cells and antigen-presenting cells (APCs) are crucial for optimal APC function, defective CD4+ T-cell activation may contribute to APC dysregulation in HIV infection. Here, we show that CD4+ T cells exposed during stimulation to noninfectious HIV having functional envelope glycoproteins failed to provide activation signals to autologous dendritic cells (DCs). Consequently, important DC functions, including production of immunoregulatory cytokines (interleukin-12 p40 and interleukin-10) and up-regulation of costimulatory molecules (CD86, CD40, CD83), as well as the capacity to stimulate naive allogeneic T cells, were all adversely affected. The blunted up-regulation of CD154 in CD4+ T cells that were activated in the presence of noninfectious viruses is likely to be the major underlying mechanism for these defects. Addition of recombinant trimeric CD154 could restore production of cytokines by DCs cocultured with HIV-exposed T cells. Moreover, the functional defects mediated by coculture with HIV-exposed T cells were similar to those following antibody blockade of CD40-CD154 interactions. HIV-mediated blunted CD154 expression may thus play an important role in the suppression of cell-mediated immunity seen in HIV infection.
Community-acquired methicillin-resistant Staphylococcus aureus orbital cellulitis in a non-immunocompromised child.

Methicillin-resistant Staphylococcus aureus (MRSA) has recently become a significant pathogen in ocular and systemic disease. 1-9 Both community- and nosocomial-acquired MRSA orbital cellulitis have been reported in adults. 1,2,3,9 However, there exist only very few published case reports of pediatric MRSA orbital cellulitis, and it is unclear whether these infections were hospital or community acquired and if these children were immunocompromised. 4,8,9 We report the first documented case of orbital cellulitis secondary to community-acquired MRSA in a non-immunocompromised child.
Safety of compressed hydrogen fuel tanks: Leakage from stationary vehicles

Abstract Compressed gas is one of the options for on-board storage of hydrogen in hydrogen-fueled vehicles. An assessment of the hazard posed by this method of storage is presented in this paper. Compressed hydrogen fuel tanks will operate under high (5000–10,000 psi) pressure and will be subject to potential failures associated with pressure vessels. In the event of a failure, hydrogen will leak through the cracks developed in these vessels, triggering an increase in the temperature, due to the negative value of the Joule–Thompson coefficient of hydrogen. The net effect of a leakage in a confined space, such as that from a vehicle parked in a garage, will be the creation of a hazardous situation, which may cause severe damage to property and human health. The potential for such hazards (from stationary vehicles) must be considered and quantified to the greatest possible extent when evaluating the various on-board hydrogen storage alternatives.
Studies on the interaction of zinc with human hemoglobin

Abstract Zn has previously been shown to increase the oxygen affinity of both normal and sickle red blood cells. Experiments are presented which demonstrate that the oxygen affinity effect of Zn is due to a Zn-hemoglobin binding mechanism rather than a Zn-2,3 diphosphoglycerate binding mechanism. Further a large shift (6 mm Hg) in the oxygen affinity of a red cell-saline suspension occurs with a low Zn/hemoglobin (tetramer) molar ratio (0.4). Zn had no influence on the Bohr effect of hemoglobin but it did decrease the Hill coefficient. Hemoglobin binding experiments using partially purified hemoglobin indicated that Zn can bind to more than one amino acid residue but it appears that the amino acid residue with the highest binding capacity for Zn is also the residue involved in the oxygen affinity effect of Zn. Hydrogen ion concentration (pH 5–8) had no influence on the Zn/hemoglobin ratios obtained in these binding experiments. The possible (and the improbable) Zn binding sites on the hemoglobin molecule are discussed.
Second-order radiometric ray tracing

Conventional ray-tracing methods fail for non-Lambertian sources. To address this deficiency, we introduce a radiometric ray-tracing (R2T) method, applicable to quasi-homogeneous sources of arbitrary spatial coherence. Based on Fourier optics, applied to physical radiometry in the radiance transfer function second-order approximation, the R2T method retains the standard ray-tracing codes but modifies them to include phase-space weighting factors attached to conventional geometric rays.
Devonian eustatic fluctuations in Euramerica

The Devonian System of Euramerica contains at least 14 transgressive-regressive (T-R) cycles of eustatic origin. These are separated into three groups (or depophases) and from Carboniferous cycles by three prominent regressions. Twelve post-Lochkovian T-R cycles are recognized, and they commonly appear to result from abrupt deepening events followed by prolonged upward shallowing. Deepening events in the western United States (especially Nevada), western Canada, New York, Belgium, and Germany have been dated in the standard conodont zonation and are demonstrably simultaneous in several or all five regions. This synchroneity indicates control by eustatic sea-level fluctuations rather than by local or regional epeirogeny. Facies shifts in shelf sedimentary successions are more reliable indicators of the timing of sea-level fluctuations than are strandline shifts in the cratonic interior, because the latter are more influenced by local epeirogeny. Strandline shifts are most useful in estimating the relative magnitude for sea-level fluctuations. Devonian facies progressions and the three prominent regressions are of a duration and an order of magnitude that could have been caused by episodes of growth and decay of Devonian oceanic ridge systems. The described T-R cycles could have formed in response to mid-plate thermal uplift and submarine volcanism. The latter process may have been a control on small-scale (1–5 m thick), upward-shallowing cycles within the major T-R cycles. Continental glaciation could have been a factor in sea-level fluctuations only in the Famennian and could not have been responsible for the Devonian facies progressions or the numerous T-R cycles. The Frasnian extinctions were apparently cumulative rather than due to a single calamity. Two rapid sea-level rises occurred just before, and one at, the Frasnian-Famennian boundary. It is probable that this series of deepening events reduced the size of shallow-shelf habitats, caused repeated anoxic conditions in basinal areas, and drowned the reef ecosystems that had sustained the immensely diverse Devonian benthos.
Rhinorrhea: A common nondopaminergic feature of Parkinson's disease†

We compared the frequency of rhinorrhea between 34 Parkinson's disease (PD) subjects and 15 normal controls (NC) and explored relationships between rhinorrhea and clinical functions, and degree of nigrostriatal dopaminergic denervation using [(11)C]dihydrotetrabenazine (DTBZ) brain positron emission tomography imaging. Sixty-eight percent (23 of 34) of PD subjects reported rhinorrhea of any cause compared with 27% (4 of 15) of NC (χ(2) = 7.07, P = 0.008). Rhinorrhea frequency remained higher in the PD group after excluding possible rhinitic etiologies: 35% (12 of 34) of PD versus 7% (1 of 15) of NC (χ(2) = 4.38, P = 0.04). There were no differences in demographics, nigrostriatal dopaminergic denervation, and clinical motor or nonmotor variables between PD subjects with and without rhinorrhea, except that more PD subjects with rhinorrhea complained of lightheadedness (52% vs. 9%, χ(2) = 5.85, P = 0.02). Rhinorrhea is a common nondopaminergic feature of PD, unrelated to olfactory or motor deficits. Further investigations are needed to determine if rhinorrhea correlates with sympathetic denervation or other autonomic symptoms in PD.
Diffuse Reflectance Studies of Solid—Solid Interactions II: Interaction of Metallic and Nonmetallic Adjuvants with Anthracene, Prednisone, and Hydrochlorothiazide

Spectral information is presented on chemisorption-diffuse reflectance studies of metallic and nonmetallic adjuvant interaction with anthracene, prednisone, and hydrochlorothiazide. The systems investigated indicate that the primary mechanism responsible for the bathochromic, hyperchromic, and visual color changes is that of charge transfer chelation.
RRR-γ-tocopherol induces human breast cancer cells to undergo apoptosis via death receptor 5 (DR5)-mediated apoptotic signaling

Goal of this study was to investigate the pro-apoptotic properties of RRR-gamma-tocopherol (gammaT) in human breast cancer cells. gammaT was shown to induce cancer cells but not normal cells to undergo apoptosis, sensitize cancer cells to Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL)-induced apoptosis, and increase death receptor 5 (DR5) mRNA, protein and cell surface expression. Knockdown of DR5 attenuated gammaT-induced apoptosis. Investigations of post-receptor signaling showed: caspase-8, Bid and Bax activation, increases in mitochondria permeability, cytochrome c release and caspase-9 activation. Thus, gammaT is a potent pro-apoptotic agent for human breast cancer cells inducing apoptosis via activation of DR5-mediated apoptotic pathway.
Education, Social Cohesion, and the Future Role of International Organizations

Although they have many important functions, The European Union, many federal governments, and the United Nations (UN) have few areas where their mandates call for them to dictate, adjudicate, or legislate education policy. Education, for the most part, has traditionally been viewed as relevant to local culture and hence subject to local control. This is now changing. Traditional interest in mathematics, science, and language remain, and although there are distinct influences drawing school systems into cross-national interests and endeavors, the main focus of attention is not on this area. Today, the main focus of attention is on the citizenship function of education, that purpose of public schooling that transcends curriculum and helps to create social cohesion, the basis of a stable democracy. This article summarizes some of the social cohesion issues involving education, the concerns over how education performs this function, and the implications for international organizations. It begins by reviewing the purposes of public education, then it discusses some
The timing of meiosis and DNA synthesis during early oogenesis in the toad, Xenopus laevis.

Recently metamorphosed female Xenopus laevis toads were injected with tritiated thymidine. Animals were kept at 20°C and were sacrificed 1–23 days after isotope injection. Radio-autographs of squash preparations of the ovaries were made. The progress of labeled germ cell nuclei was followed to obtain information on the time course of early meiosis and extra-chromosomal DNA synthesis. Premeiotic S was estimated to take not more than 7 days. Leptotene takes 4 days, zygotene takes 5 days, and pachytene was estimated to be completed in about 18 days. The major period of amplification of the extrachromosomal DNA occurs in pachytene and takes about 13 days. A low level of synthesis was observed before and after this period, in zygotene and late pachytene-early diplotene, extending the total time for extrachromosomal DNA synthesis during meiosis to about 18 days. These data allowed the calculation to be made that one round of replication of the amplified DNA takes between 1.2 and 3.0 days. It was also found that in both oogonial and premeiotic interphases, the nucleolus-associated DNA shows asynchronous (probably late) labeling with respect to the chromosomes.
Evaluation of the microangiographic fluoroscope (MAF) using generalized system performance metrics.

Purpose: The performance of a newly developed, high resolution, microangiographic fluoroscope (MAF) (35 μm pixel pitch and 300 μm thick CsI phosphor) was evaluated using a generalized linear system analysis and compared with that of a standard amorphous Si thin film transistor flat panel detector (FPD) (194 μm pixel pitch and 600 μm thick CsI phosphor). The linear system metrics such as modulation transfer function (MTF), noise power spectrum, and detection quantum efficiency (DQE) are commonly used to gauge the intrinsic detector performance in the detector plane. However, these linear system metrics do not provide information about the image receptor performance in a real system since they do not include the effects of other parameters such as focal spot distribution, scatter radiation, and geometric unsharpness, which may compromise detector performance characteristics. Use of generalized linear system metrics [generalized modulation transfer function (GMTF), generalized normalized noise power spectrum (GNNPS), and generalized detection quantum efficiency (GDQE)] that include these effects gives a more meaningful, complete, and appropriate evaluation of detector performance as part of the imaging system. Methods: A uniform head equivalent phantom was used to simulate realistic clinical parameters and x-ray spectra. The detector MTFs were measured using the slanted edge method and the focal spot MTFs were measured using a pinhole assembly. The scatter MTF was simulated and the scatter fraction was measured for a head-equivalent phantom. The generalized system metrics were calculated for different combinations of three choices of focal spots and three different magnifications with two different air-gaps. The performance of the MAF was also illustrated using stent images obtained with different focal spots under similar conditions. Results: Results for the generalized metrics provide a quantitative description of the performance of the imaging system for both detectors. This generalized analysis demonstrated that both detectors have similar imaging capabilities at lower spatial frequencies, but that the MAF has superior performance over the FPD at higher frequencies even when considering focal spot blurring and scatter. Conclusions: This generalized performance analysis demonstrates the significance of focal spot size, magnification, and scatter on the system performance metrics (GMTF, GNNPS, and GDQE). Although the ideal detector performance characteristics of the MAF are not fully realized due to these other system factors, it still retains an advantage in DQE at high spatial frequencies over the FPD. Similar studies based on the generalized linear system metrics can serve as an efficient tool to evaluate total system capabilities under different realistic conditions to enable optimal design for specific imaging tasks.
Pathogenesis of simian varicella virus.

Simian varicella virus (SVV) is closely related to varicella-zoster virus (VZV) and induces a natural varicella-like disease in nonhuman primates. Therefore, simian varicella is a useful model to investigate varicella pathogenesis and to evaluate antiviral therapies. In this report, we review recent studies on SVV pathogenesis and latency. Experimental infection of African green monkeys is followed by a 7-10 day incubation period during which a viremia disseminates the virus throughout the body. Clinical disease is characterized by fever and vesicular skin rash. Pneumonia and hepatitis may occur during more severe infections. Examination of acutely infected tissues reveals histopathology including necrosis and hemorrhage in the skin, lung, liver, and spleen. In contrast, the neural ganglia exhibit minimal histopathology. SVV DNA, immediate early, early, and late gene transcripts, and viral antigens are detected in the tissues of acutely infected monkeys. Host immune responses are induced which resolve the acute infection within 21 days. During or after acute infection, SVV establishes latent infection in the ganglia of surviving monkeys. The virus may reactivate later in life to cause secondary disease and viral transmission to susceptible monkeys.
Auditory/Verbal hallucinations, speech perception neurocircuitry, and the social deafferentation hypothesis.

Auditory/verbal hallucinations (AVHs) are comprised of spoken conversational speech seeming to arise from specific, nonself speakers. One hertz repetitive transcranial magnetic stimulation (rTMS) reduces excitability in the brain region stimulated. Studies utilizing 1-Hz rTMS delivered to the left temporoparietal cortex, a brain area critical to speech perception, have demonstrated statistically significant improvements in AVHs relative to sham simulation. A novel mechanism of AVHs is proposed whereby dramatic pre-psychotic social withdrawal prompts neuroplastic reorganization by the “social brain” to produce spurious social meaning via hallucinations of conversational speech. Preliminary evidence supporting this hypothesis includes a very high rate of social withdrawal emerging prior to the onset of frank psychosis in patients who develop schizophrenia and AVHs. Moreover, reduced AVHs elicited by temporoparietal 1-Hz rTMS are likely to reflect enhanced long-term depression. Some evidence suggests a loss ...
Effects of non-ideal switches in PWM switching converters

This paper presents new models that account for the non-ideal properties of semiconductor BJT switches responsible for the switching action in PWM converters. These models can be used for both the DC and small-signal AC analyses of PWM switching regulators. Terminal voltages and currents of the switching elements of the converter are related using switching functions which account for the non-ideal characteristics of the semiconductor switches, such as delay, rise, storage, fall and reverse recovery times. Models have been derived and used in DC and AC small-signal analysis of the three basic topologies: buck, boost, and buck-boost converters operating in the continuous conduction mode. The switching times of the semiconductor switches result in a change of the duty cycle which affects both the DC and small-signal performance of the converters. The change in the DC conversion ratio due to the switching times is shown for the three converters. It is also shown that a resistance is introduced into the AC mo...
Immunolocalization of pericentriolar material in algal mitotic spindles

Double-label immunofluorescence of tubulin and preicentriolar material (PCM) was carried out with mitotic nuclei in the coenocytic green alga Ernodesmis. Spindle poles are heavily labeled with serum 5051 (anti-PCM) from midprophase through mid- to late anaphase, and bright fluorescence is also evident at the tips of the elongated interzonal spindle in telophase nuclei. Very faint labeling with anti-PCM is also detected throughout the spindle (and/or its matrix) at all mitotic stages. Control treatments demonstrated that nonspecific surface labeling of chloroplasts with anti-PCM may be due to some naturally occurring component of human sera rather than to specific labeling by the anti-PCM serum. Ultrastructural work indicates that the centrosome is always associated with spindle poles through anaphase, but not with the tips of the interzonal telophase Immunoper-oxidase electron microscopy verifies that anti-PCM labels the centrosomes of mitotic nuclei in these cells. However, labeling is also present inside the presistent nuclear envelope at the spindle poles, during metaphase, anaphase, and at the tips of the interzonal spindles. Regions of heaviest labeling correspond with amorphous material near the centrioles and at the spindle poles, as evident in conventional electron microscope preparations. The origin of intranuclear amorphous material that labels with anti-PCM is unclear, but the ends of many spindle microtubules are embedded in it, especially at anaphase, and the tips of microtubules near the amorphous material are often labeled with the antiserum. These results indicate for the first time that serum 5051 does indeed label PCM at the poles of centric spindles in plant cells. Although the location of the labeled material suggests it is associated with the nucleation of spindle microtubules, this conclusion requires more information about microtubule dynamics in these cells. Caution is also warranted in interpreting variant anti-PCM labeling patterns in other plant cells because of spurious labeling of the spindle itself and other cytoplasmic organelles.
Restoration of scanning-tunneling-microscope data blurred by limited resolution, and hampered by 1 /ƒ-like noise

Least-squares or Wiener filters are powerful tools to restore blurred and noisy pictures. For an optimal implementation, a knowledge of the noise and of the point-spread function (PSF) is needed; whereas the resolution PSF is relatively well known from recent theories of STM, the noise spectrum can be investigated by recording and analyzing the signal of the feedback which should keep the tunneling current constant. A 1fβ noise spectrum is found with β = 1.4 ± 0.2. This noise can give rise to pretended hills and valleys or to spurious stripes parallel to the scanning direction in STM images. With a Wiener filter, in which the model noise-to-signal ratio is 1fβ-like, these artificial features are eliminated. However, since the noise spectrum may partly overlap the desired spectrum of the surface corrugation, care has to be taken not to generate new artifacts.