cssi/SciSciGPT-SciSciNet huggingface dataset:
Targeted disruption of the Oct-2 locus in a B cell provides genetic evidence for two distinct cell type-specific pathways of octamer element-mediated gene activation.

Abstract The Oct-2 protein is a tissue-specific POU-homeodomain transcription factor. It has been considered to represent a developmental regulator of immunoglobulin gene expression by virtue of its interaction with a functionally essential octamer element found in immunoglobulin gene promoters. This proposal has been most strongly challenged by several in vitro transcription analyses which have shown that the related ubiquitous factor Oct-1 can activate transcription from immunoglobulin gene promoters as efficiently as Oct-2. We have genetically analyzed Oct-2 function by using gene targeting to disrupt both alleles of the locus in the murine B cell line WEHI-231. This cell line expresses productively rearranged immunoglobulin genes as well as the Oct-2 gene at high levels which are comparable to those observed in activated murine splenic B cells. In spite of a drastic reduction in Oct-2 levels (20-fold), no effect was observed on the expression of endogenous immunoglobulin genes or on the activity of a transfected immunoglobulin promoter or a heterologous promoter with a single octamer element. In contrast, expression of a reporter construct containing multiple octamer motifs upstream of a heterologous promoter was severely reduced in the double-disruptant cells. The differential responses of the single- and multiple-octamer motif reporter constructs in the mutant B cells are unlikely to be a consequence of differing concentration requirements for activation by Oct-2. The two constructs are activated equivalently over the same range of Oct-2 concentration in a non-B cell. These results provide genetic support for the existence of an Oct-2-independent, but octamer element-dependent, B cell-specific pathway for immunoglobulin gene transcription. They also genetically reveal a distinct Oct-2-dependent pathway of octamer-mediated gene activation. This study demonstrates the feasibility of targeting a diploid locus in a somatic mammalian cell line. Extension of this approach to genes encoding other transcription factors will allow a genetic dissection of their functions within the context of cell lines representing various differentiation states.
E-051 Intracranial aneurysm classification scale optimized for treatment device indications and contraindications

Introduction Aneurysm classification is typically based upon midline-dome diameter (size) and occasionally utilizes other parameters such as midline-dome diameter to neck diameter ratio (d:n ratio) and neck diameter (figure 1). Size classifications are typically oriented around the aneurysm’s risk of rupture, and the classification ranges are often inconsistent between sources. While the current classification system still serves a significant role, we propose a more comprehensive and consistent classification system that considers multiple dimensions/parameters and allows surgeons, regulatory bodies, and medical device developers to quickly identify suitable treatment devices for patient-specific aneurysm dimensions and morphologies. Materials and methods A meta-analysis of both intracranial aneurysm studies and papers outlining aneurysm classification systems provided data regarding aneurysm dimensions, correlation of aneurysm dimensions to treatment failure rates of endovascular devices, and the current state of aneurysm classification systems. This data was then used to create an intracranial aneurysm classification system that is optimized to help predict the success or failure of certain types of endovascular intracranial aneurysm treatments. Results and discussion While there is a correlation between aneurysm size and the outcome of certain aneurysm treatment devices, there are other parameters that are equally as impactful on the treatment outcome, such as midline diameter (d), neck diameter (n), and the ratio between them (d:n ratio) (Figure 1). Neck diameter and d:n ratio both had significant effects on treatment outcome for certain devices, even though aneurysm size (dome height) is often the only dimension referenced. Conclusions While aneurysm size can be an important indicator for both aneurysm rupture and treatment outcome, there are other parameters that also have a significant impact on treatment success. These additional parameters, such as midline diameter, neck diameter and the d:n ratio, should be carefully considered when choosing a device for treatment, developing a device, or approving devices into the market. The proposed classification system in this study has the potential to help close the research gap between the different classification systems that practitioners, developers, and regulators may apply to intracranial aneurysms. Disclosures W. Merritt: 1; C; NIH, Northern Arizona University. T. Becker: 1; C; NIH, Northern Arizona University. A. Ducruet: 1; C; NIH, Northern Arizona University. 5; C; Barrow Neurological Institute.
Calibration reveals limitations in modeling rainfall interception at the storm scale

Abstract Rainfall interception by the forest canopy plays an important role in the water budget by removing water from the terrestrial hydrologic cycle as an atmospheric loss. Effective models of canopy interception are critical for simulating the water budget and river flows. Over the years, several models have been developed to simulate canopy interception. Few comparative studies have been conducted that assess how well these models simulate measured interception. This study compared five mechanistic canopy interception models including the Rutter, Rutter Sparse, Gash, Gash Sparse, and Liu models. The objective of the study was to use an objective automatic calibration to compare how the models behave relative to each other. The objective of the study was not to establish definitive optimal parameter sets. Each interception model was calibrated independently using the Parameter Estimation and Uncertainty Analysis program (PEST), an automatic parameter estimation routine. The five models were calibrated using field measurements from an eastern deciduous forest dominated by American beech and yellow-poplar under leafed and leafless conditions. The models performed well in predicting cumulative interception, with errors ranging between 0.0% and 14.9%. However, model performance declined when assessing individual rainfall events where the coefficient of determination (R2) between measured and modeled interception events ranged between 0.21 and 0.48. The models were unable to simulate very low or very high levels of interception. Measured interception ranged between 0.2 and 12.2 mm while modeled interception only ranged between 1.2 and 6.9 mm. The inability of the models to satisfactorily simulate measured interception is likely due to: 1) errors in parameter ranges, 2) measurement errors, and/or 3) a fundamental misunderstanding of interception mechanics. These results indicate an important gap in our ability to understand a substantial portion of the water budget.
Multiple Primary Malignant Neoplasms: An Unusual Case of Metachronous Breast Ductal and Squamous Cell Carcinomas

Multiple primary malignant neoplasms (MPMN) are generally defined as the co-occurrence of multiple primary malignant neoplasms of distinct histology in the same individual. Second and higher-order primary malignancies now comprise about 18% of all incidence of cancer in the USA. The incidence ratio of developing multiple primary cancers (MPCs) in female cancer survivors is 1.17 to 1.6. In women with breast cancer, the incidence ratio is even higher, according to age at diagnosis of breast cancer. However, the concurrence of breast cancer and squamous cell carcinoma is not described in the literature. Primary squamous cell carcinoma of bone is also rare in the skeletal system other than in the skull, with only three such cases reported in the English literature. We present a case of a 59-year-old woman with high-grade primary invasive ductal carcinoma of the breast and second distinct squamous cell carcinoma metastasis to the bone of unknown primary site. A search for a primary squamous cell carcinoma, including CT head and neck, CT chest, colposcopy, esophagogastroduodenoscopy (EGD) and colonoscopy, did not show any evidence of a primary site.
The Toughest Triage - Allocating Ventilators in a Pandemic.

The Toughest Triage Of all the medical care that will have to be rationed during the Covid-19 pandemic, the most problematic will be mechanical ventilation. One strategy for avoiding debilitating d...
The 2008 Crisis

This chapter briefly summarizes how we got to the 2008 crisis and what human factors shaped the formation of the 2008 crisis, also called the Great Recession. Some of these factors were already-known sides of human nature, which were mentioned in the literature of other disciplines. The crisis reminded us our sides economics and finance have long ignored.
Novel renal medullary carcinoma cell lines, UOK353 and UOK360, provide preclinical tools to identify new therapeutic treatments

Renal medullary carcinoma (RMC) is a rare, aggressive disease that predominantly afflicts individuals of African or Mediterranean descent with sickle cell trait. RMC comprises 1% of all renal cell carcinoma diagnoses with a median overall survival of 13 months. Patients are typically young (median age-22) and male (male:female ratio of 2:1) and tumors are characterized by complete loss of expression of the SMARCB1 tumor suppressor protein. Due to the low incidence of RMC and the disease's aggressiveness, treatment decisions are often based on case reports. Thus, it is critical to develop preclinical models of RMC to better understand the pathogenesis of this disease and to identify effective forms of therapy. Two novel cell line models, UOK353 and UOK360, were derived from primary RMCs that both demonstrated the characteristic SMARCB1 loss. Both cell lines overexpressed EZH2 and other members of the polycomb repressive complex and EZH2 inhibition in RMC tumor spheroids resulted in decreased viability. High throughput drug screening of both cell lines revealed several additional candidate compounds, including bortezomib that had both in vitro and in vivo antitumor activity. The activity of bortezomib was shown to be partially dependent on increased oxidative stress as addition of the N-acetyl cysteine antioxidant reduced the effect on cell proliferation. Combining bortezomib and cisplatin further decreased cell viability both in vitro and in vivo that single agent bortezomib treatment. The UOK353 and UOK360 cell lines represent novel preclinical models for the development of effective forms of therapy for RMC patients.
Perspectives of Patients with Pre-existing Mobility Disability on the Process of Diagnosing Their Cancer.

Mobility disability is the most common disability among adult Americans, estimated at 13.7% of the US population. Cancer prevalence is higher among people with mobility disability compared with the general population, yet people with disability experience disparities in cancer screening and treatment. We explored experiences of patients with mobility disability with the process of cancer diagnosis. Open-ended individual interviews, which reached data saturation. Interviews were transcribed verbatim for conventional content analysis. We interviewed 20 participants with pre-existing mobility disability that required the use of an assistive device or assistance with performance of activities of daily living and who were subsequently diagnosed with cancer (excluding melanoma). Concerns coalesced around five broad categories: inaccessibility of medical diagnostic equipment affecting the process of cancer diagnosis, attitudes of clinical staff about accommodating disability, dismissal of cancer signs/symptoms as emotional responses to chronic health conditions, misattributing cancer signs/symptoms to underlying disability, and attitudes about pursuing legal action for substandard care. Participants provided examples of how erroneous assumptions and potentially biased attitudes among clinicians interfered with the process of their cancer diagnosis, sometimes contributing to an insufficient workup and diagnostic delays. Physical and attitudinal barriers affect the process of cancer diagnosis in people with mobility disability. Though people with mobility disability may be clinically complex, clinicians should be aware of the risks of diagnostic overshadowing (i.e., the misattribution of cancer signs/symptoms to underlying disability) and other erroneous assumptions that may affect timeliness of cancer diagnosis and quality of care. Further efforts, including educating clinicians about challenges in caring for persons with disability, should be considered to improve the process of cancer diagnosis for this population. N/A
Friendly or unfriendly confines: impact of Chicago baseball stadia on vicinity crime patterns

The purpose of this paper is to explore the impact of the two Major League Baseball stadia in Chicago, Wrigley Field and Guaranteed Rate Field (GRF) on stadium vicinity crime to assess changes in c...
Epilogue: The Poet as Scientist; The Scientist as Poet

In this chapter, I offer eight biosemiotic concepts or principles and then eight corresponding sets of writing prompts, the idea being to help readers explore the biosemiotic connections between nature and culture, semiosis and writing, and science and literature. As Kalevi Kull has written, biosemiotics is “all about” “finding the poetic or poetic-like processes in living systems” (Biosemiotics 10:17, 2017); therefore, good biosemioticians understand the artfulness of nature itself; and good poets and practitioners of biosemiotic criticism understand the need for powerful modes of scientific analysis.
Comparing electrocatalytic and thermocatalytic conversion of nitrate on platinum–ruthenium alloys

Nitrate is a significant water pollutant resulting from anthropogenic nitrogen fixation and other industrial processes. Heterogeneous thermocatalytic and electrocatalytic processes to convert nitrate to nitrogen or ammonia are proposed to follow similar reaction mechanisms. However, there are no studies comparing these two processes on the same catalyst surface under similar reaction conditions. Here, we study both reactions on a series of PtxRuy/C alloys to identify similarities and differences. For both reactions, we find that catalyst activity is correlated to both hydrogen and nitrate adsorption energies, signifying the importance of hydrogen and nitrate coverage in both systems. We show that PtRu catalysts, recently reported to enhance electrocatalytic nitrate reduction, are also more active for thermocatalytic nitrate reduction than Pt. However, the effect of pH on reaction rates is considerably different between the two reactions, indicating that electrochemical-specific steps differentiate the two processes. We analyze the cost of converting nitrate to ammonia through both thermocatalytic and electrocatalytic reduction under different conditions on the same catalyst to compare which process is more cost-effective and capable of approaching the rates of commercial Haber–Bosch ammonia production.
Comorbid Substance Abuse and Mental Illness

Abstract Literature concerning assessment and treatment of comorbid substance abuse and mental illness is reviewed. Currently, comorbidity is under-diagnosed and dually diagnosed clients are under-served. Those clients, who are so diagnosed, are most often offered dichotomous parallel or serial interventions. However, research suggests that an integrated approach is preferable. Enhanced training of mental health and substance abuse professionals is urgently needed as is further research concerning the efficacy of various treatment modalities. Improved identification and treatment of comorbidity may reduce the revolving door effect among these individuals and thereby lower health care costs.
Prothrombinase complex assembly. Kinetic mechanism of enzyme assembly on phospholipid vesicles.

The kinetics of the assembly of the prothrombinase complex was studied using factor Xa modified with the active site-directed fluorophore dansylglutamylglycylarginyl chloromethyl ester (DEGR.Xa) as a reporter for the process. Stopped-flow kinetic studies of prothrombinase assembly were undertaken at saturating concentrations of calcium ion, using vesicles composed of phosphatidylcholine and phosphatidylserine (PCPS), factor Va, and DEGR.Xa. The rate of complex formation, studied under pseudo first-order conditions, depended on the premixing protocol used to initiate complex assembly and was most rapid when prothrombinase assembly was initiated by reacting Va with the preformed DEGR.Xa.PCPS complex. Under these conditions, reaction rate was linearly dependent on the concentration of PCPS with no evidence for saturation and was independent of the concentration of VA. Essentially identical reaction rates were observed when the association of Va with PCPS was independently assessed by stopped-flow light scattering. The data indicate that prothrombinase assembly initiated by mixing Va with the DEGR.Xa.PCPS complex is rate limited by the initial reaction between Va and available combining sites on the vesicle surface (k = 5.7 x 10(7) M-1.s-1) followed by extremely rapid reactions (k greater than 1 x 10(9) M-1.s-1) between PCPS-bound DEGR.Xa and PCPS-bound Va. The formation of a separate Va.PCPS complex is therefore required for prothrombinase assembly to proceed. Reaction rates obtained when prothrombinase assembly was initiated by reacting DEGR.Xa with the preformed Va.PCPS complex or by reacting PCPS with a mixture of DEGR.Xa and Va were lower. Under these initiation conditions, reaction rates were inhibited by increasing concentrations of factor Va. These data indicate that the formation of the DEGR.Xa.PCPS binary complex is also a prerequisite for prothrombinase assembly. The second-order rate constant for the reaction between factor Xa and PCPS (k = 2.9 x 10(7) M-1.s-1) and the first-order rates of dissociation of the Va.PCPS complex (koff = 0.17 s-1) and the Xa.PCPS complex (koff = 3.3 s-1) were independently determined by stopped-flow light scattering. Collectively, the data are consistent with the interpretation that prothrombinase assembly proceeds via the initial formation of separate Xa.PCPS and Va. PCPS binary complexes at near diffusion-limited rates on the same vesicle. The lipid-bound constituents then react rapidly via rearrangements on the vesicle surface to form prothrombinase.
The 2009 exceptional Amazon flood and interannual terrestrial water storage change observed by GRACE

[1] The Gravity Recovery and Climate Experiment (GRACE) satellite gravity mission provides a new capability for measuring extreme climate events, such as floods and droughts associated with large‐scale terrestrial water storage (TWS) change. GRACE gravity measurements show significant TWS increases in the lower Amazon basin in the first half of 2009, clearly associated with the exceptional flood season in that region. The extended record of GRACE monthly gravity solutions reveals the temporal and spatial evolution of both nonseasonal and interannual TWS change in the Amazon basin over the 7 year mission period from April 2002 to August 2009. GRACE observes a very dry season in 2002–2003 and an extremely wet season in 2009. In March 2009 (approximately the peak of the recent Amazon flood), total TWS surplus in the entire Amazon basin is ∼624 ± 32 Gt, roughly equal to U.S. water consumption for a year. GRACE measurements are consistent with precipitation data. Interannual TWS changes in the Amazon basin are closely connected to ENSO events in the tropical Pacific. The 2002–2003 dry season is clearly tied to the 2002–2003 El Nino and the 2009 flood to the recent La Nina event. The most significant contribution of this study in the area of water resources is to confront the hydrological community with the latest results of the GRACE satellite mission and further demonstrates the unique strength of GRACE and follow‐up satellite gravity observations for measuring large‐scale extreme climate events.
The boson method in superconductivity: Application to the study of the Josephson effect

The boson method in superconductivity is applied to the study of the Josephson effect. This approach permits us to calculate all the important observable quantities, like the magnetic field and the current, at any point of the system, without making’ use of any phenomenological assumption, such asJ =j1 sinϕ. The results of our calculation show a qualitative agreement with those computed by other authors on the basis of the Josephson equation, though we do not have and we do not use this equation. The boson method is also able to yield results for a neutral superconductor, so that the calculations can be applied to the analogous effects that can be found in superfluid liquids. Finally, we would like to point out that our results do not necessarily satisfy the phenomenological equationJ =j1 sinϕ.
Power System Security

The sections in this article are 1 Security Assessment 2 Security Assessment Techniques 3 Conclusion
Polarization-strain coupling and relaxor behavior of KxLi1-xTaO3

Abstract It is shown that the characteristic relaxor behavior of KLT is due to the collective π/2 reorientations of off-center lithium ions in the highly polar host KTaO3. The reorientation provides a simple microscopic mechanism for the coupling of polarization and strain as manifested by the striking dielectric resonances observed in KLT.
Polymer optical fibers for photonics

Polymer optical fibers may suitable for a wide variety of applications because they are easy to process into a wide variety of structures. For example, graded index fibers are widely believed to be ready for high bandwidth local area network applications such as fiber to the home. The polymer graded index fiber is inexpensive, easy to splice, and insensitive to small misalignment at a connector. Single mode polymer optical fibers, on the other hand, are promising candidates for all-optical devices because of the high light intensitities they can support, ability to tailor materials to meet a given application, and ease of fiber fabrication. In this paper, we review methods to make polymer fibers, discuss the fabrication process that is used to make graded-index fibers, single-mode polymer fibers and more complex fiber structures such as dual-core fibers. We also describe linear and nonlinear characterization techniques and review fiber properties. In particular, we discuss refractive index profile measurements in both graded index and step index fiber preforms, waveguiding studies in dual-core optical fibers, nonlinearity, and loss. We also introduce a new class of devices that are based on the photomechanical effect and discuss characterization studies and demonstration devices.
Effect of Dehydroepiandrosterone on Muscle Strength and Physical Function in Older Adults: A Systematic Review

OBJECTIVES: To evaluate studies that have assessed the effect of dehydroepiandrosterone (DHEA) supplementation on body composition and physical performance in older adults. DESIGN: A systematic review of the medical literature identified from searches of databases, reference lists, and recent conference proceedings with qualitative assessment of the desired end points. SETTING: Not applicable. PARTICIPANTS: Adults aged 50 and older. INTERVENTIONS: Oral DHEA supplement with or without concomitant exercise. MEASUREMENTS: Muscle strength, physical function, and physical performance. RESULTS: Of the 155 eligible studies, eight (n=661 participants) met inclusion criteria. The studies differed in their included populations, duration of follow-up, and interventions (e.g., exercise). Seven studies examined measures of muscle strength. One study showed improvement in handgrip strength, one showed improvement in chest press, two showed improvement in leg press, and one showed improvement in knee extension and flexion. Nevertheless, similar numbers of studies had negative results for each of these endpoints. Five studies examined measures of physical function and performance. Only one study showed improvement in a composite score measuring physical performance; the rest reported no differences between DHEA and control for any end point. CONCLUSION: Overall, the benefit of DHEA on muscle strength and physical function in older adults remains inconclusive. Some measures of muscle strength may improve, although consensus was not reached. DHEA does not appear to routinely benefit measures of physical function or performance. Further large clinical trials are necessary to better identify the clinical role of DHEA supplementation in this population.
Autosomal recessive inheritance of airway hyperreactivity to 5-hydroxytryptamine

We have previously reported that airway hyperresponsiveness to acetylcholine (ACh) is inherited as an autosomal recessive trait in A/J and C3H/HeJ mice and the progeny of crosses between them (FASE...
The interlamellar atomic habit plane in Cu-6% Be pearlite

Abstract This investigation has sought to gain a better understanding of interphase boundaries in lamellar solid-solid phase transformations. Transmission electron microscopy has been used to characterize the f.c.c./ordered b.c.c. interface in the eutectoid Cu-6% Be binary. The atomic habit plane is established to be (111)f.c.c.//(110)b.c.c. with [110]f.c.c.//[111]b.c.c. Direction steps similar to those described by Hackney and Shiflet in ferrous pearlites were the only interfacial defect observed. Using point group intersection theory and our experimental results, it is shown that although the atomic habit plane is not a symmetry-dictated energy extremum, it is a minimum in energy space.
High Reliability System Design Experience with the Gamma Ray Large Area Space Telescope

The Large Area Telescope (LAT) is the primary instrument on the Gamma Ray Large Area Space Telescope (GLAST), a space based observatory which is scheduled to launch late this year. The LAT traces its heritage from the particle physics community and represents a large departure in design and capability from previous space based experiments. Similarly, power, communication, and physical access limitations of a space based platform place strict requirements on the design and reliability of both the LAT and its Trigger and Dataflow (T&DF) system. The resulting T&DF system consists of a hierarchical trigger with both Level 0 and Level 3 components, distributed event processing, and slow control. We describe our experiences developing and testing the T&DF system in the context of a space mission, and we report the performance and status of the system as GLAST approaches launch.
Development of a simple, rapid and reproducible HPLC assay for the simultaneous determination of hypericins and stabilized hyperforin in commercial St. John's Wort preparations

Abstract A reversed-phase HPLC method was developed and validated for the simultaneous determination of hypericins and stabilized hyperforin in St. John's Wort extract. The sample solution was prepared by extraction of the finely powdered extract with methanol–water (80:20, v/v) containing 5% HP-β-cyclodextrin, and adjusted to pH 2.5 with orthophosphoric acid. Diluted extract solutions, maintained at 0 °C, were injected into a C18 column. The samples were eluted isocratically using a mobile phase consisting of acetonitrile and 0.3% v/v phosphoric acid (90:10, v/v) at a 1.5 ml/min flow rate with simultaneous fluorescence (315/590 nm, excitation/emission) and UV (273 nm) detection. Quantification of the marker compounds (hypericin, pseudohypericin, hyperforin) was achieved by use of standard curves generated by plotting peak heights versus concentrations. Validation studies demonstrated that this HPLC method is simple, rapid, reliable, and reproducible. The standard curves were linear over the concentration ranges, 0.5–2.5 μg/ml (hypericin), 0.35–1.6 μg/ml (pseudohypericin) and 5–50 μg/ml (hyperforin). The intra-day coefficients of variation obtained for hypericin, pseudohypericin and hyperforin were ⩽4.4%, ⩽5.4%, and ⩽2.8%, respectively; inter-day CVs were ⩽5.8%, ⩽4.9%, and ⩽2.5%, respectively. This method may be applied for the routine standardization of St. John's Wort products against hyperforin and the hypericins, the putative antidepressant principles in the herbal.
R invariance and axion cosmology

Abstract Conditions under which an R symmetry is a cosmologically acceptable Peccei-Quinn symmetry are found. These conditions are then imposed on specific models and severe constraints on the number of generations in these models are found.
Cathode lens electron microscopy: past and future

This retrospective sketches the evolution of emission electron microscopy, low energy electron microscopy and related methods from the early stages up to the present state and gives a brief outlook on the future possibilities of these cathode lens electron microscopy techniques. It is concerned mainly with instrumentation, discusses some little known work and emphasizes important steps in the evolution of the field instead of attempting to review it in detail.
Synthesis of an iron(II)-braced proline-II tripod protein

This paper describes the engineering of braced tripod proteins for use as molecular frameworks. Specifically, a 30-residue tripod-shaped protein with three proline-II helical legs braced by an iron(II)tris(bipyridine) complex was modularly designed, chemically synthesized, and biophysically characterized. Three copies of a 10-residue leg peptide were covalently linked through sulfide bonds to an N-terminal apex (1,3,5-tris(methylene)benzene) and by amide bonds to the brace (FeII (Mbc)3: Mbc is 4′-methyl-2,2′-bipyridine-4-carbonyl). The leg peptide (H-Cys-Pro5-Pra(Mbc)-Pro3-NH2: Pra iscis-4-amino-l-proline) was assembled by the solid-phase method using Boc-Pra(Mbc)-OH, which was synthesized in 75% overall yield by coupling Mbc-OH to the 4-amino group of Boc-Pra-OCH3 and saponifying the methyl ester group. The iron(II)-braced tripod was assembled by S-alkylation of three copies of the leg peptide with 1,3,5-tris(bromomethyl)benzene followed by ligation of Fe2+ to the resulting unbraced tripod. The CD spectrum of the iron(II)-braced tripod showed a positive MLCT band at 570 nm and a negative π-π* band at 312 nm, so its FeII(Mbc)3 brace was predominantly in the Δ configuration. In a mostly acetonitrile solution at 25°C, the leg peptide and the unbraced tripod isomerized from the proline-II helical form into the proline-I helical form but the iron(II)-braced tripod remained in the proline-II helical form.
Scalable, example-based refactorings with refaster

We discuss Refaster, a tool that uses normal, compilable before-and-after examples of Java code to specify a Java refactoring. Refaster has been used successfully by the Java Core Libraries Team at Google to perform a wide variety of refactorings across Google's massive Java codebase. Our main contribution is that a large class of useful refactorings can be expressed in pure Java, without a specialized DSL, while keeping the tool easily accessible to average Java developers.
Distributed sensory coding applied to simulations of iconic storage and metacontrast

If information is coded in the combination of activities of many neurons operating in parallel, then information present in a network can be defined by the correlation of present network activity with the activity which had been elicited by a stimulus in the past; a high correlation indicates the presence of the previously encoded stimulus. Information is distributed in the network because coding is dependent upon the activities of all cells. A model based on Hartline-Ratliff lateral inhibition with a time delay shows that lateral inhibition can distribute information across a parallel network, reduce output noise, and also briefly store information. With no changes in model parameters, and the use of a correlation measure for recognition, the model can stimulate psychophysical results in eleven variations of the metacontrast masking paradigm.
Time-accurate analysis of nonequilibrium gas-particle mixtures using upwind/implicit finite-volume methodology

A new Eulerian particulate solver whose numerical formulation is compatible with the numerics in state-of-the-art finite-volume upwind/implicit gas dynamic computer codes is presented. The heat transfer, drag, thermodynamic, and phase-change procedures in this code are derived from earlier, well established data fits and procedures. Performance for numerous flow problems with one- and two-way coupling is quite good. The solutions are nonoscillatory and robust and conserve flux balances very well. 18 refs.
Feature analysis for the NIITEK ground-penetrating radar using order-weighted averaging operators for landmine detection

An automated methodology for combining Ground Penetrating Radar features from different depths is presented and analyzed. GPR data from the NIITEK system are processed by a depth-dependent, adaptive whitening algorithm. Shape and contrast features, including compactness, solidity, eccentricity, and relative area are computed at the different depths. These features must be combined to make a decision as to the presence of a landmine at a specific location. Since many of the depths contain no useful information and the depths of the mines are unknown, a strategy based on sorting is used. In a previous work, sorted features were combined via a rule-based system. In the current paper, an automated algorithm that builds a decision rule from sets of Ordered Weighted Average (OWA) operators is described. The OWA operator sorts the feature values, weights them, and performs a weighted sum of the sorted values, resulting in a nonlinear combination of the feature values. The weights of the OWA operators are trained off-line in combination with those of a decision-making network and held fixed during testing. The combination of OWA operators and decision-making network is called a FOWA network. The FOWA network is compared to the rule-based method on real data taken from multiple collections at two outdoor test sites.
Development and characterization of a TES optical imaging array for astrophysics applications

Our research group has successfully developed photon detectors capable of both time-stamping and energy-resolving individual photons at very high rates in a wide band from the near-IR through optical and into the near-UV. We have fabricated 32-pixel arrays of these Transition-Edge Sensor (TES) devices and have mounted them in an adiabatic demagnetization refrigerator equipped with windows for direct imaging. We have characterized single pixel behavior; we have also begun operating multiple pixels simultaneously, starting the scaling process towards use of the full array. We emphasize the development of a metalized mask for our array that blocks photons from hitting the inter-pixel areas and reflects them onto the TESs. We also present calibration data on detector resolution, electronics noise, and optical alignment.
Workers' participation and control in Italy: the case of occupational medicine.

This article sets forth a historical and current analysis of (a) the occupational health services in Italy; and (b) the political, economic, and social forces that determined them. Special focus is placed on the analysis of the events leading to the establishment in 1969 of forms of direct democracy at the workplace, i.e. workers' committees, and their consequences for the occupational health services. Also described and analyzed are the responsibilities and modus operandi of these committees in the creation and reproduction of scientific knowledge at the point of production. The relationship between the workers' committees, the "experts," and the institutions of medicine, as well as that between the workers' committees, political parties, and the trade unions, is also discussed. An update on the impact that recent political developments have had on these workers' committees concludes the article.
Batch scheme recursive parameter estimation of continuous-time systems using the modulating functions method

Abstract The modulating functions method is a very effective method for parameter estimation of continuous time systems that are linear in their parameters. One efficient implementation developed by Pearson and Lee involves the use of trigonometric functions and fast computations offered by FPT techniques. In this paper, a recursive implementation of the method is developed for on-line parameter estimation of a continuous-time system by shifting a fixed window of time series data one step forward at each sampling instant. The resulting recursion algorithms are fast, and use the identities of discrete Fourier transforms along with some inherent commutative properties. A simulation example with a Van der Pol oscillator is included to investigate the performance of the proposed estimation method.
Leading the way: The role of presidents and academic deans in fundraising

Although professional staff can assist with parts of the fundraising enterprise, presidents and deans play the leading role in cultivating and soliciting major gifts to benefit the academic enterprise.
Preconditioning-mimetics bradykinin and DADLE activate PI3-kinase through divergent pathways.

Abstract We previously reported that pharmacological preconditioning of rabbit hearts with acetylcholine involves activation of phosphatidylinositol 3-kinase (PI3-K) through transactivation of the epidermal growth factor receptor (EGFR). Transactivation is thought to be initiated by cleavage of membrane-bound pro-heparin-binding EGF-like growth factor (HB-EGF) by a membrane metalloproteinase thus releasing HB-EGF which binds to the EGFR. This pathway leads to redox signaling with the generation of reactive oxygen species (ROS) by mitochondria. We tested whether preconditioning's physiological triggers, bradykinin and opioid, also signal through the EGFR. Both bradykinin and the synthetic δ-opioid agonist DADLE increased ROS production in isolated cardiomyocytes by approximately 50%. DADLE's effect was abrogated by either metalloproteinase inhibitor III (MPI) or the diphtheria toxin mutant CRM-197 which blocks heparin-binding EGF shedding indicating that DADLE signals through EGFR transactivation. MPI also blocked DADLE's infarct-sparing effect in whole hearts. Additionally, blocking Src kinase (a component of the EGFR's signaling complex) with PP2 or PI3-K with wortmannin blocked DADLE's effect on cardiomyocyte ROS production and PP2 blocked DADLE's salvage of ischemic myocardium. Finally, DADLE increased phosphorylation of Akt and extracellular signal-regulated protein kinases (ERK) 1/2 in left ventricular myocardium, and this increase was blocked by the EGFR antagonist AG1478. On the other hand, neither MPI nor CRM-197 prevented bradykinin from increasing ROS production, and MPI did not affect bradykinin's infarct-sparing effect in intact hearts. Conversely, both PP2 and wortmannin blocked bradykinin's effect on ROS generation and also aborted bradykinin's cardioprotective effect in intact hearts. While bradykinin also increased phosphorylation of Akt and ERK in myocardium, that increase was not affected by AG1478. Hence bradykinin, unlike acetylcholine or opioid, does not transactivate EGFR, although all 3 agonists do signal through Src and PI3-K.
A kinetic analysis and replication of decreased platelet serotonin uptake in depressed patients

Platelet serotonin uptake was kinetically measured in 32 psychiatric inpatients and 32 age- and sex-matched controls. Patients were categorized into four groups: depressed patients, manic bipolars, other affective disorders, and nonaffective psychiatric disorders. A randomized block factorial analysis of variance indicated that the depressed patients had a significantly lower maximal velocity (Vmax) of serotonin uptake in comparison to matched controls, without a statistically significant difference in Km. No statistically significant difference was found for any of the other diagnostic groups in comparison to controls for Vmax or Km. These results are compared with previous studies of platelet serotonin transport in clinically depressed patients and in physostigmine-induced depression.
Using CFD Surface Solutions to Shape Sonic Boom Signatures Propagated from Off-Body Pressure

The conceptual design of a low-boom and low-drag supersonic aircraft remains a challenge despite significant progress in recent years. Inverse design using reversed equivalent area and adjoint methods have been demonstrated to be effective in shaping the ground signature propagated from computational fluid dynamics (CFD) off-body pressure distributions. However, there is still a need to reduce the computational cost in the early stages of design to obtain a baseline that is feasible for low-boom shaping, and in the search for a robust low-boom design over the entire sonic boom footprint. The proposed design method addresses the need to reduce the computational cost for robust low-boom design by using surface pressure distributions from CFD solutions to shape sonic boom ground signatures propagated from CFD off-body pressure.
Striatal Kinetic Modeling of FDOPA with a Cerebellar-Derived Constraint on the Distribution Volume of 3OMFD: A PET Investigation using Non-Human Primates

The peripherally born metabolite of FDOPA, 3-O-Methyl-FDOPA (3OMFD), crosses the blood-brain barrier, thus complicating positron emission tomography-FDOPA (PET-FDOPA) data analysis. In previous reports the distribution volume (DV) of 3OMFD was constrained to unity. We have recently shown that the forward transport rate-constant of FDOPA (K(S1)) and the cerebellum-to-plasma ratio (C(b)/C(p)), a measure for the DV of 3OMFD, are functions of plasma large neutral amino acid (LNAA) concentration. Given large interstudy and intersubject differences in plasma LNAA levels, variations in the DV of 3OMFD are significant. In this report, the authors propose a constraint on the DV of 3OMFD that accounts for these variations. Dynamic PET-FDOPA scans were performed on 12 squirrel monkeys and 12 vervet monkeys. Two sets of constraints were employed on the compartmental model--M1 or M2. In M1, the striatal DV of 3OMFD was constrained to unity; in M2, the striatal DV of 3OMFD was constrained to an estimate derived from the cerebellum. Striatal and cerebellar time-activity curves were fitted using FDOPA and 3OMFD plasma input functions. The estimate of K(S1) and that of the compartmental FDOPA uptake-constant (K(i)), both obtained using M2, were adjusted to values corresponding to average LNAA levels. Finally, K(i) was compared with the graphical uptake-constant (PK(j)). With the use of constraint M2, intersubject variability of squirrel monkey k(S3) and K(i) was reduced by 45% and 53%, respectively; and for vervet monkeys, by 54% and 44%, respectively. Intersubject variability of K(1) and K(i) was further reduced after correction for variations in intersubject plasma LNAA levels (for squirrel monkeys, by 67% and 41%; for vervet monkeys, by 40% and 36%, respectively). K(i) correlation to PK(i) was enhanced to identity. Finally, average cerebellar k(C2) estimates were more than 2.5-fold higher than striatal k(S2) estimates (P < 0.0001). In modeling of PET-FDOPA data, it cannot be assumed that the DV of 3OMFD is unity. The cerebellar-derived constraint furnishes a reliable estimate for the DV of 3OMFD. Invoking the constraint and correcting for variations in plasma LNAA significantly reduced interstudy and intersubject variations in parameter estimates.
Classical Mathematical Models for Description and Prediction of Experimental Tumor Growth

Despite internal complexity, tumor growth kinetics follow relatively simple laws that can be expressed as mathematical models. To explore this further, quantitative analysis of the most classical of these were performed. The models were assessed against data from two in vivo experimental systems: an ectopic syngeneic tumor (Lewis lung carcinoma) and an orthotopically xenografted human breast carcinoma. The goals were threefold: 1) to determine a statistical model for description of the measurement error, 2) to establish the descriptive power of each model, using several goodness-of-fit metrics and a study of parametric identifiability, and 3) to assess the models' ability to forecast future tumor growth. The models included in the study comprised the exponential, exponential-linear, power law, Gompertz, logistic, generalized logistic, von Bertalanffy and a model with dynamic carrying capacity. For the breast data, the dynamics were best captured by the Gompertz and exponential-linear models. The latter also exhibited the highest predictive power, with excellent prediction scores (≥80%) extending out as far as 12 days in the future. For the lung data, the Gompertz and power law models provided the most parsimonious and parametrically identifiable description. However, not one of the models was able to achieve a substantial prediction rate (≥70%) beyond the next day data point. In this context, adjunction of a priori information on the parameter distribution led to considerable improvement. For instance, forecast success rates went from 14.9% to 62.7% when using the power law model to predict the full future tumor growth curves, using just three data points. These results not only have important implications for biological theories of tumor growth and the use of mathematical modeling in preclinical anti-cancer drug investigations, but also may assist in defining how mathematical models could serve as potential prognostic tools in the clinic.
A phase I pharmacodynamic trial of bortezomib in combination with doxorubicin in patients with advanced cancer.

Purpose This phase I trial sought to define the toxicity, maximally tolerated dose (MTD) and pharmacodynamics of a combination of bortezomib and doxorubicin in patients with advanced malignancies.
Comparison of tricalcium phosphate cement and cancellous autograft as bone void filler in acetabular fractures with marginal impaction

Abstract Objective To compare clinical and radiological outcome between acetabular fractures with marginal impaction that were treated with either cancellous bone graft (CBG) or tricalcium phosphate cement (TPC) as bone void filler. Design Retrospective study. Patients Forty-three patients with acetabular fractures with marginal impaction. Intervention Eighteen patients received cancellous bone graft and 25 patients received tricalcium phosphate cement as bone void filler. Main outcome measurement Clinical outcome was assessed using the Merle d’Aubigne score and Short-form-36. Radiographs were evaluated for postoperative reduction, arthritis grade and development of heterotopic ossification. Results Forty-three patients met the inclusion criteria. There was no significant difference in the demographics, laterality, fracture type, associated injuries, surgical approach and postoperative quality of reduction between the groups. At final follow-up, a significantly higher number of patients in the cancellous bone graft group exhibited signs of moderate to severe post-traumatic arthritis (CBG: 6 (33%) vs. TPC: 4 (20%), p = 0.007) and required a total hip arthroplasty (CBG: 4 (22.2%) vs. TPC: 1 (5%), p = 0.08). There was no significant difference between the two groups in the SF-36 score and the modified Merle d’Aubigne score. Conclusion Patients with acetabular fractures with marginal impaction treated with tricalcium phosphate cement exhibit a significantly lower incidence of post-traumatic arthritis when compared to patients treated with cancellous bone graft. Level of evidence III.
Variation in the relationship between gestational diabetes diagnosis and total gestational weight gain by race/ethnicity

Prior research suggests that women diagnosed and treated for gestational diabetes mellitus (GDM) gain less total gestational weight than normoglycemic women. Our study finds that race/ethnicity modifies this association. Relative to normoglycemic women, non-Hispanic white women with GDM gain less weight but non-Hispanic black and Hispanic women gain more weight.