cssi/SciSciGPT-SciSciNet huggingface dataset:
Biomarkers for personalized oncology: recent advances and future challenges

Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells and oncology is a branch of medicine that deals with tumors. The last decade has seen significant advances in the development of biomarkers in oncology that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression. Clinical molecular diagnostics and biomarker discoveries in oncology are advancing rapidly as we begin to understand the complex mechanisms that transform a normal cell into an abnormal one. These discoveries have fueled the development of novel drug targets and new treatment strategies. The standard of care for patients with advanced-stage cancers has shifted away from an empirical treatment strategy based on the clinical-pathological profile to one where a biomarker driven treatment algorithm based on the molecular profile of the tumor is used. Recent advances in multiplex genotyping technologies and high-throughput genomic profiling by next-generation sequencing make possible the rapid and comprehensive analysis of the cancer genome of individual patients even from very little tumor biopsy material. Predictive (diagnostic) biomarkers are helpful in matching targeted therapies with patients and in preventing toxicity of standard (systemic) therapies. Prognostic biomarkers identify somatic germ line mutations, changes in DNA methylation, elevated levels of microRNA (miRNA) and circulating tumor cells (CTC) in blood. Predictive biomarkers using molecular diagnostics are currently in use in clinical practice of personalized oncotherapy for the treatment of five diseases: chronic myeloid leukemia, colon, breast, lung cancer and melanoma and these biomarkers are being used successfully to evaluate benefits that can be achieved through targeted therapy. Examples of these molecularly targeted biomarker therapies are: tyrosine kinase inhibitors in chronic myeloid leukemia and gastrointestinal tumors; anaplastic lymphoma kinase (ALK) inhibitors in lung cancer with EML4-ALk fusion; HER2/neu blockage in HER2/neu-positive breast cancer; and epidermal growth factor receptors (EGFR) inhibition in EGFR-mutated lung cancer. This review presents the current state of our knowledge of biomarkers in five selected cancers: chronic myeloid leukemia, colorectal cancer, breast cancer, non-small cell lung cancer and melanoma.
Structures of two classes of MHC molecules elucidated: crucial differences and similarities

New structures of MHC molecules have significantly improved our understanding of molecular recognition in cellular immunology. Highlights include the first structure of a class II MHC molecule, complexed with a viral peptide and with a bacterial superantigen. A structure of an MHC-like Fc receptor is expected soon. Interesting comparisons can now be made between the recognition properties of MHC and MHC-like proteins.
A Qualitative Study in a Rural Community: Investigating the Attitudes, Beliefs, and Interactions of Young Children and Their Parents Regarding Storybook Read Alouds

This qualitative study describes the physical and verbal interactions of rural children and their parents regarding reading books aloud. The participants’ attitudes and beliefs about sharing storybooks are also explored. The theoretical framework is based upon Bronfenbrenner’s Ecological Model. One interview was conducted with each participant and video recorded. An observation of one book sharing session for each dyad was conducted and video recorded. The Adult/Child Interactive Reading Inventory (ACIRI) (DeBruin-Parecki 2004, 2007) was used during analysis of the observations. Narrative analysis was utilized. Themes and categories emerged from the data. The self-report of each participant was compared to the observation. Overall, the interview data were in alignment with the observed interactions.
Trends in and determinants of outcomes in multi-union certification elections

We use data on 68,000 single-union and 3,600 multi-union elections during the years 1977–1994 to investigate factors influencing outcomes of multi-union elections. We find that, even though the win rate is much higher in multi-union as opposed to singleunion elections, the factors influencing the outcomes are surprisingly similar.
Correlation of capacitance and actuation in ionomeric polymer transducers

Ionomeric polymer transducers are electromechanical actuators fabricated from ion-exchange membranes that have been surface plated with conductive metal. In this paper we discuss a series of experiments that characterize the electromechanical actuation response of three families of ionomers: Nafion (a product of DuPont), BPSH (sulfonated poly(arylene ether sulfone)) and PATS (poly(arylene thioether sulfone)). The first polymer is commercially-available while the second and third polymers are synthesized by the direct polymerization of sulfonated monomers in our lab. The mechanical properties and actuation response of Nafion-117, BPSH, and PATS of varying ionic content are studied in the Lithium cation form. The strain response of the materials varies from 50 μ strain/V to 750 μ strain/V at 1Hz. A linear correlation was found between the strain response and the capacitance of the material. This correlation was independent of the polymer composition and the plating parameters. All of the ionomers analyzed in this work exhibited a strain-to-charge response between 9 \(\frac{\rm \mu strain}{\frac{C}{\rm m^2}}\) and 15 \(\frac{\rm \mu strain}{\frac{C}{\rm m^2}}\). Due to the fact that the low-frequency capacitance of an ionomer is strongly related to charge accumulation at the blocking electrodes, this correlation suggests a strong relationship between surface charge accumulation and mechanical deformation in ionomeric actuators.
Soliton quantization in chiral models with vector mesons

Abstract A canonical quantization of the skyrmion with ω-mesons is presented using Dirac theory of quantization under constraints. After removing the spurious spin-isospin zero modes from the meson spectrum, an explicit meson-nucleon hamiltonian is constructed. In the strong ω-coupling limit the semi-classical results are recovered. The relevance of this approach to low-energy meson-nucleon physics is stressed.
The impact of multi-institutional semi-structured learning environments (MISSLE)

A specific instance of the multi-institutional semi-structured learning environment (MISSLE) informing system construct is introduced and described. The description places an emphasis on aspects that have proven successful in accelerating new systems to the customer and in the enhancement of systems for those participating in these collaborative learning events. Examples are provided that include unmanned/robotic systems, command and control systems, and surveillance/reconnaissance systems.
Transplantation of free tibial periosteal grafts for the repair of articular cartilage defect: An experimental study.

Background: Articular chondrocytes have got a long lifespan but rarely divides after maturity. Thus, an articular cartilage has a limited capacity for repair. Periosteal grafts have chondrogenic potential and have been used to repair defects in the articular cartilage. The purpose of the present study is to investigate the differentiation of free periosteal grafts in the patellofemoral joint where the cambium layer faces the subchondral bone and to investigate the applicability of periosteal grafts in the reconstruction of articular surfaces. Materials and Methods: The study was carried out over a period of 1 year on 25 adult, male Indian rabbits after obtaining permission from the institutional animal ethical committee. A full-thickness osteochondral defect was created by shaving off the whole articular cartilage of the patella of the left knee. The defect thus created was grafted with free periosteal graft. The patella of the right knee was taken as a control where no grafting was done after shaving off the articular cartilage. The first animal was used to study the normal histology of the patellar articular cartilage and periosteum obtained from the medial surface of tibial condyle. Rest 24 animals were subjected to patellectomy, 4 each at serial intervals of 2, 4, 8, 16, 32 and 48 weeks and the patellar articular surfaces were examined macroscopically and histologically. Results: The grafts got adherent to the underlying patellar articular surface at the end of 4 weeks. Microscopically, graft incorporation could be appreciated at 4 weeks. Mesenchymal cells of the cambium layer were seen differentiating into chondrocytes by the end of 4 weeks in four grafts (100%) and they were arranged in a haphazard manner. Till the end of 8 weeks, the cellular arrangement was mostly wooly. At 16 weeks, one graft (25%) had wooly arrangement of chondrocytes and three grafts (75%) had columnar formation of cells. Same percentage was maintained at 32 weeks. Four grafts (100%) at 48 weeks showed columnar orientation. The control side showed no changes over the shaved off articular surface in all the rabbits. One rabbit at 4 weeks had a dislocation of the patella on the control side. None of the rabbits developed any infection or wound dehiscence. Conclusion: Autologous periosteal graft transplantation can be a promising substitute for articular cartilaginous defects.
Offense-Defense Theory and Its Critics

The author thanks Michael Desch, Charles Glaser, Stanley Hoffmann, Andrew Kydd, John Mearsheimer, Daniel Philpott, Bradley Thayer, Karen Turato, Stephen Van Evera, Celeste Wallander, participants in a seminar at the Center for International Relations, University of California at Los Angeles, and two anonymous reviewers for their helpful comments on previous drafts of this article. An earlier version of this article was delivered at the 1995 Annual Convention of the International Studies Association, Chicago, Illinois, 21–25 February 1995.
Phenotypic differentiation in female preference related to geographic variation in male predation risk in the Trinidad guppy (Poecilia reticulata)

Populations of the Trinidad guppy range from areas with high levels of predation by other species of fish to areas with little or no piscine predation. Previous studies have shown that variation among populations in male coloration can be explained by a balance between female preference for brighter males and natural selection against bright males. High levels of male courtship activity may also increase both predation risk and mating success. Therefore, in high-predation areas, females that mate with males that court frequently as well as those that choose bright males would presumably produce male offspring with low survivorship. Consistent with this variation in natural selection, we observed that females from high-predation populations were less likely to choose bright and frequently courting males than females from low-predation populations. This result supports the hypothesis that female preference is evolving as a character genetically correlated with the preferred male character, in which case higher levels of natural selection acting against the male character should be related to lower levels of female preference.
Nonexponential statistics of fluorescence photobleaching

In this paper, I consider theoretical models of the decay via photobleaching of a sample of surface-immobilized fluorescent molecules excited by a spatially varying laser intensity profile. I show that, with mild restrictions on the photobleaching mechanism, the fluorescence decay measured in a nonuniform excitation profile is always nonexponential. Under the same conditions, the fluorescence decay can always be approximated by a discrete sum of exponentials. A particular example is given in which a homogeneous population of fluorophores with a single (intensity-dependent) photobleaching lifetime, when illuminated by a Gaussian laser, exhibits power law fluorescence decay at long times. These results indicate that the observation of multiple exponentials in single molecule or ensemble photobleaching lifetime measurements can arise solely as an artifact of a spatially varying laser profile and is not necessarily indicative of heterogeneity in molecular internal states, conformation, or local environment.
CdS thin films formed on flexible plastic substrates by pulsed-laser deposition

The merger of a transparent plastic foil substrate with a semiconductor CdS film for a photonic application was realized using pulsed-laser deposition. Although plastic is not considered to be a favoured substrate material for semiconductor thin-film formation, the deposited CdS film possesses good adhesion, with a polycrystalline texture, flat surface (roughness/thickness = 0.003), and room-temperature photosensitivity with a blue-shifted peak at 2.54 eV. This work demonstrates the capability of pulsed-laser deposition to form novel heterostructures with appealing and useful technological properties such as plasticity and low weight.
Does incentive compensation lower executives' willingness to take risks?

The article reports on a study by Randolph P. Beatty and Edward J. Zajac concerning initial public offerings (IPO), risk exposure, and executive compensation. The researchers found that executives at firms that are strategically risky were less likely to accept non-cash incentives such as stock options because of the risk associated with holding the corporation's stock. Alternative governance mechanisms are used to monitor top management including independent directors on the corporate board and venture capital backing. An amendment to the United States Internal Revenue Code Section 162m is criticized for its potential to inhibit entrepreneurship.
Electroluminescence of InAs-GaSb heterodiodes

The electroluminescence of a Type II InAs-GaSb superlattice heterodiode has been studied as a function of injection current and temperature in the spectral range between 3 and 13 /spl mu/m. The heterodiode comprises a Be-doped midwavelength infrared (MWIR) superlattice with an effective bandgap around 270 meV and an undoped long wavelength infrared (LWIR) superlattice with an effective bandgap of 115 meV. At high injection currents and elevated temperatures the band to band transitions of both superlattices can be observed. By increasing the temperature the intensity of the MWIR emission component shows a well defined thermally activated increase. The activation energy of the Beryllium doping was evaluated to be 28 meV.
Big Five traits interact to predict perceived social support

Many studies have examined the simple bivariate associations between the Big Five personality traits and perceived availability of social support. The current study examined whether any of the Big Five traits interacted to predict perceived support. Participants (N = 366) completed a Big Five personality inventory and a measure of perceived social support. Extraversion, neuroticism and openness predicted overall social support. These same three traits interacted to predict perceived support. That is, at low levels of extraversion, low neuroticism was associated with greater perceived support irrespective of level of openness. However, as extraversion increased, the combination of low neuroticism and low openness was associated with the greatest level of perceived support. At high levels of extraversion, high neuroticism and low openness was associated with the lowest level of perceived support. Implications of these findings are discussed.
L'article Seignor ’Schwiegervater’ dans I‘ Altfranzösisches Wörterbuch

(1982). L'article Seignor ’Schwiegervater’ dans I‘ Altfranzosisches Worterbuch. Studia Neophilologica: Vol. 54, No. 1, pp. 99-108.
Romanian reform movement in the 1980s: Fundamental changes in the making?

(1983). Romanian reform movement in the 1980s: Fundamental changes in the making? Nationalities Papers: Vol. 11, No. 1, pp. 41-61.
CAP: an automated self-assessment tool to check Pascal programs for syntax, logic and style errors

Student programmers have difficulty finding and fixing syntax, logic and style errors in their programs. The Code Analyzer for Pascal (CAP) analyzes programs that use a subset of the Pascal language and provides user-friendly feedback on the errors that it finds. This paper describes CAP and reports its use in teaching introductory programming at the United States Air Force Academy.
Risk factor implications of incidentally discovered uncomplicated bundle branch block.

OBJECTIVE To evaluate the long-term outcome of a community-based patient population with incidentally discovered asymptomatic and uncomplicated bundle branch block (BBB). PATIENTS AND METHODS A retrospective observational cohort study was undertaken of patients in Olmsted County, Minnesota, who were evaluated between 1975 and 1999 and were incidentally diagnosed as having BBB. We performed Kaplan-Meier analyses of all-cause mortality and development of first cardiac morbidity after the diagnosis of BBB, along with matched control group comparisons. RESULTS A total of 723 patients with left BBB (LBBB) (58.1%) and right BBB (41.9%) met criteria. Mortality was higher in patients with BBB compared with controls (absolute difference of approximately 10% over 20 years; hazard ratio=1.27; confidence interval, 1.02–1.58; P =.03) as was the development of first cardiac-related morbidity (hazard ratio=1.32; confidence interval, 1.14–1.54; P P =.02). However, comparable mortality was shown between patients with BBB who did not have these risk factors and matched control patients who had these risk factors. The risk of developing cardiac-related morbidity also was increased in the presence of BBB, particularly LBBB. CONCLUSIONS Uncomplicated asymptomatic BBB (notably LBBB) with normal left ventricular ejection fraction is not benign. Our findings indicate that the presence of isolated BBB denotes a high-risk patient subgroup that has a compromised long-term outcome comparable to patients with conventional cardiovascular risk factors.
Confocal mosaicing microscopy of human skin ex vivo: spectral analysis for digital staining to simulate histology-like appearance

Confocal mosaicing microscopy enables rapid imaging of large areas of fresh tissue, without the processing that is necessary for conventional histology. Mosaicing may offer a means to perform rapid histology at the bedside. A possible barrier toward clinical acceptance is that the mosaics are based on a single mode of grayscale contrast and appear black and white, whereas histology is based on two stains (hematoxylin for nuclei, eosin for cellular cytoplasm and dermis) and appears purple and pink. Toward addressing this barrier, we report advances in digital staining: fluorescence mosaics that show only nuclei, are digitally stained purple and overlaid on reflectance mosaics, which show only cellular cytoplasm and dermis, and are digitally stained pink. With digital staining, the appearance of confocal mosaics mimics the appearance of histology. Using multispectral analysis and color matching functions, red, green, and blue (RGB) components of hematoxylin and eosin stains in tissue were determined. The resulting RGB components were then applied in a linear algorithm to transform fluorescence and reflectance contrast in confocal mosaics to the absorbance contrast seen in pathology. Optimization of staining with acridine orange showed improved quality of digitally stained mosaics, with good correlation to the corresponding histology.
Experimental Studies of Separation on a Two-Dimensional Airfoil at Low Reynolds Numbers

The laminar separation, transition, and turbulent reattachment near the leading edge of a two-dimensional NACA 663 -018 airfoil were investigated using a low-speed, smoke visualization wind tunnel. Lift and drag force measurements were made using an external strain gage balance for a chord Reynolds number range of 40,GOO400,000. An extensive flow visualization study was performed and correlated with the force measurements. Experiments were also conducted with distributed surface roughness at the leading edge and external acoustic excitation to influence the development of the airfoil boundary layer. This study delineates the effects of angle of attack and chord Reynolds number on the separation characteristics and airfoil performance. Nomenclature c = model chord cd = section profile drag coefficient (uncorrected) cf = section lift coefficient (uncorrected) Cp = pressure coefficient / = acoustic frequency, Hz R = reattachment location Rc = Reynolds number based on chord length, U^ civ S = separation location T = location of approximate end of transition £/«, = freestream velocity x/c = nondimensional distance along chord a = angle of attack v - kinematic viscosity
Modulation of the neuronal nicotinic acetylcholine receptor-channel by the nootropic drug nefiracetam.

Abstract The effects of nefiracetam (DM-9384) on the neuronal nicotinic acetylcholine (ACh) receptor-channel were studied by the whole-cell patch clamp technique using PC12 cells. Nefiracetam had a dual effect on ACh-induced currents: it augmented the currents induced by low concentrations (10–30 μM) of ACh and suppressed those induced by high concentrations (100–1000 μM) of ACh. These effects were reversible after washing with drug-free solution. The stimulating effect of nefiracetam was clearly observed at a concentration of 10 μM, and slight increases in currents were detected even at 0.1 μM or 1 μM. Nefiracetam at 100 μM suppressed the currents induced by a low concentration (10 μM) of ACh. The rate of desensitization of ACh-induced current was greatly accelerated by nefiracetam, and this effect could not be reversed by washing with drug-free solution. When added to the internal pipette solution, the protein kinase A inhibitor KT 5720 (0.6 μM), but not the protein kinase C inhibitor calphostin C (0.5 μM), abolished the nefiracetam stimulation of the ACh receptor. Pre-incubation of cells with 200 ng/ml pertussis toxin for 24 h also abolished the nefiracetam action. Thus, the nefiracetam modulation of the neuronal nicotinic ACh receptor-channel is exerted via G proteins and protein kinase A. The stimulation of the ACh receptor may be directly related to the cognitive enhancing action of nefiracetam.
Room-temperature imprinting method for plastic microchannel fabrication

A new plastic imprinting method using a silicon template is demonstrated. This new approach obviates the necessity of heating the plastic substrate during the stamping process, thus improving the device yield from ∼10 devices to above 100 devices per template. The dimensions of the imprinted microchannels were found to be very reproducible, with variations of less than 2%. The channel depths were dependent on the pressures applied and the materials used. Rather than bonding the open channels with another piece of plastic, a flexible and adhesive poly(dimethylsiloxane) film is used to seal the microchannels, which offers many advantages. As an application, isoelectric focusing of green fluorescence protein on these plastic microfluidic devices is illustrated.
Development of Pleistophora sp. (Microsporidian) in eggs of the polychaete Armandia brevis

Abstract The development of Pleistophora sp. is followed from a plasmodial stage to mature spores. In every stage studied dikarya were encountered. The plasmodium is densely populated by ribosomes and smooth endoplasmic reticulum. Sporoblasts form by the development of a space between the plasmodium and host cell while, within the plasmodium, large vesicles arise. These vesicles fuse to separate sporoblasts each with a dikaryon. In the sporoblasts the polar filament and polar cap develop from Golgi membranes. The cytoplasm of spores is very compact. Apically the polaroplast surrounds the polar cap while basally the tandem elements of the dikaryon are still recognizable.
Direct Penetration of Cell-Penetrating Peptides Across Lipid Bilayers

The short, charged, amphipathic and sometimes structured cell-penetrating peptides (CPPs) have been shown promising carriers for delivering protein, RNA, DNA, and even nanoparticles into cells. The mechanistic understanding of how CPPs cross the cell membrane and what biophysical property is critical for efficient penetration is nevertheless largely unknown, mostly due to the lack of proper experimental tools to directly assess the penetration process.In order to gain insights in the universal rules of penetration mechanism of CPPs, we selected six peptides from three different classes of proposed mechanisms: (1) Tat and poly-arginine as structurally “disordered”, cationic peptides that most likely enter the cell via endocytosis; (2) penetratin and pVEC as beta-stranded amphipathic peptides shown capable of directly translocate through the membrane; and (3) TP10 and modeled amphipathic peptide (MAP) as alpha-helical amphipathic peptides also being able to penetrate directly. We have developed new techniques based on atomic force microscopy (AFM) to measure energetic and dynamic properties as CPPs go through the bilayer. CPPs were attached via thiol-gold linkage to Au-coated AFM probes and brought into contact with lipid bilayers. The displacement-time trajectory of CPPs inside the bilayers was directly measured during bilayer breakthroughs under different force loading rates. Biophysical characteristics, such as potential energy barrier of bilayer failure, dynamics of penetration pathways, and bilayer structural rearrangement, were derived and compared among the six peptides, which will lead to new classification of CPPs sharing distinguishable biophysical traits.
WE-A-BRB-08: Dosimetric Investigation of Praseodymium-142 Microspheres for Microsphere Brachytherapy of Nonresectable Hepatic Tumor

Purpose: To evaluate the dosimetric parameters of Praseodymium‐142 (1 4 2Pr) glass microspheres and its potential application in microsphere brachytherapy of nonresectable hepatic tumor for faster dose delivery and facilitated quality assurance, while maintaining comparable dose distribution of the currently used radionuclides. Methods:Dose profiles for a 1 4 2Pr point source were obtained using BRAIN‐DOSE dose point kernel code and MCNPX2.6 Monte Carlo simulation. Microspheres containing 14 2Pr were studied and their dose distributions were compared to the doses of the currently used radionuclide Yittrium‐90 (9 0Y). Dose distributions due to glass microspheres ensembles within different sizes of spherical tumors were simulated. Physical properties, e.g. time to deliver 90% of the total dose for 1 4 2Pr and 9 0Y, were studied. Results:Dose rates from BRAIN‐ DOSE calculation for ‘ 1 4 2Pr and 9 0Y were 4.42 mGy/hr and 5.53 mGy/hr at 0.5 cm away from a 1 μCi source. From MCNPX2.6 the beta dose per decay at the tumor center for 142Pr and 9 0Y were 2.02 × 10−12 Gy and 2.36 × 10−12 Gy, respectively, for a tumor of 2.5 cm radius. For this case, simulation showed that the total dose in the tumor vicinity and therefore to adjacent organs due to the gamma yield was small, e.g. 0.03 Gy at 10 cm from the tumor center for 150 Gy total physical dose.Conclusions: Total dose per decay due to beta emissions were similar for both 1 4 2Pr and 9 0Y. Shorter half‐life is an advantage of ‘ 1 4 2Pr, enabling faster dose delivery. The physical properties of 1 4 2Pr make it suitable for microsphere brachytherapy. Total gamma contribution of 1 4 2Pr was small, therefore may not be clinically relevant. Gamma radiation, however, opens possibilities for quality assurance, biodistribution imaging and dose distribution assessments.
Protein for Lp82 calpain is expressed and enzymatically active in young rat lens.

mRNA for a newly discovered isoform of calpain, termed Lp82, was recently discovered in young rat lens. The purpose of the present experiments was to test for expression of Lp82 protein. Casein zymography after incubation with calcium was used to detect Lp82 proteolytic activity in regions of lenses from young rats. Lp82 protein was detected by immunoblotting or by ELISA after DEAE-5PW chromatography using a polyclonal antibody generated to a peptide sequence in Lp82. Northern blot analysis assessed expression of Lp82 mRNA. Four results demonstrated expression of Lp82 protein; (1) immunoblot reactivity at the predicted molecular mass of 82 kDa, (2) a unique band of calcium-activated lysis in casein zymograms, (3) partial purification and retention of activity from a single Lp82 peak on DEAE-5PW chromatography, and (4) positive immunoblotting and Northern blot analysis only in lens and not in other rat tissues. These results showed that Lp82 protein is lens-preferred, relatively abundant in young rats (especially nucleus), and enzymatically active. Proteolysis of crystallins in the nucleus of young rat lens during normal maturation and cataract formation, formerly attributed solely to m-calpain, may in fact be due to concerted action of both lens Lp82 and ubiquitous m-calpain.
Dynamic forecasting of urban shopping travel demand

Abstract A time-dependent model for commercial activity location and travel demand is developed based on the assumptions that instantaneous interzonal shopping travel demand can be described by a gravity formulation, whereas the incremental individual zonal retail space allocations are such that they maximize the aggregate, net resulting profit from retail sales. Over time, link travel costs are updated as a function of the current link volumes, whereas commercial space development costs are updated as a function of current zonal activity levels. Constraints on commercial space allocation are at the individual zonal level, as well as at the aggregate level of the overall area. The objective function for the corresponding mathematical program is then linearized, and the model programmed for implementation using a linear programming routine. The results of several simulations illustrate the dynamic impacts various urban development policies have on commercial activity location. In particular, periodic oscillations in zonal activity levels, as well as sudden changes in the spatial pattern of interzonal shopping travel, may appear for certain model parameter values. Several directions for future refinement of the model, including inclusion of economic variables and interaction with other urban activities, are discussed in conclusion.
Non-invasive imaging of beta cell mass: a quantitative analysis.

BACKGROUND: Currently there are major efforts to develop strategies for the in vivo imaging of pancreatic beta cell mass as a clinical and investigational tool for detecting and tracking the loss of beta cells that underlies the progression of Type I diabetes. However, beta cells constitute only about 1% of pancreatic mass and are distributed throughout the pancreas within tiny islets of Langerhans that are each less than the spatial resolution of non-invasive imaging technologies. METHODS: To estimate the requisite binding characteristics of a candidate beta cell imaging agent, calculations of the beta cell contribution to a positron emission tomography signal were made using simple equations. These were based on the relative population of beta cells and non-beta cells within the pancreas and surrounding tissue and an equation describing equilibrium ligand binding. RESULTS: The calculations show that two criteria must be met: (1) The low-volume fraction of beta cells within the exocrine pancreas (about 1:100) requires that beta cells retain labeled imaging agents at least 1,000-fold more strongly than exocrine cells. (2) Agents that label cell surface receptors, even if beta cell-specific, must do so at a high enough level so that the imaging signal arising from unbound label retained in extracellular spaces must not overwhelm signals from labeled beta cells. CONCLUSIONS: The limits developed here can serve as criteria for identifying candidate imaging agents for the in vivo imaging of beta cell mass, thereby avoiding expensive preclinical development using compounds that have no chance of success. (Less)
Modulation of innate immunity by Toxoplasma gondii virulence effectors

Toxoplasma gondii is a common parasite of animals and humans and can cause serious opportunistic infections. However, the majority of infections are asymptomatic, possibly because the organism has co-evolved with its many vertebrate hosts and has developed multiple strategies to persist asymptomatically for the lifetime of the host. Over the past two decades, infection studies in the mouse, combined with forward-genetics approaches aimed at unravelling the molecular basis of infection, have revealed that T. gondii virulence is mediated, in part, by secretion of effector proteins into the host cell during invasion. Here, we review recent advances that illustrate how these virulence factors disarm innate immunity and promote survival of the parasite.
Immobilized Artificial Membranes — screens for drug membrane interactions

Abstract Immobilized Artificial Membranes (IAMs) are monolayers of phospholipid analogs covalently bonded to the surface of silica particles. 31P NMR and molecular dynamics (MD) simulations demonstrated that IAMs and liposome membranes exhibit similar interfacial properties. These similar interfacial properties have resulted in IAMs' being useful as a physico-chemical model of drug-membrane partitioning. IAM chromatography has been successful used to predict: (1) solute partitioning into liposome membranes; (2) drug permeability through Caco-2 cells; (3) drug intestinal absorption; (4) brain uptake of amino acids; (5) bile salt-membrane interactions; and (6) human skin permeability of steroids and alcohols. In addition, IAM chromatography has also been used to obtain hydrophobicity parameters for SAR studies.
Inertial stochastic dynamics. I. Long-time-step methods for Langevin dynamics

Two algorithms are presented for integrating the Langevin dynamics equation with long numerical time steps while treating the mass terms as finite. The development of these methods is motivated by the need for accurate methods for simulating slow processes in polymer systems such as two-site intermolecular distances in supercoiled DNA, which evolve over the time scale of milliseconds. Our new approaches refine the common Brownian dynamics (BD) scheme, which approximates the Langevin equation in the highly damped diffusive limit. Our LTID (“long-time-step inertial dynamics”) method is based on an eigenmode decomposition of the friction tensor. The less costly integrator IBD (“inertial Brownian dynamics”) modifies the usual BD algorithm by the addition of a mass-dependent correction term. To validate the methods, we evaluate the accuracy of LTID and IBD and compare their behavior to that of BD for the simple example of a harmonic oscillator. We find that the LTID method produces the expected correlation structure for Langevin dynamics regardless of the level of damping. In fact, LTID is the only consistent method among the three, with error vanishing as the time step approaches zero. In contrast, BD is accurate only for highly overdamped systems. For cases of moderate overdamping, and for the appropriate choice of time step, IBD is significantly more accurate than BD. IBD is also less computationally expensive than LTID (though both are the same order of complexity as BD), and thus can be applied to simulate systems of size and time scale ranges previously accessible to only the usual BD approach. Such simulations are discussed in our companion paper, for long DNA molecules modeled as wormlike chains.
Lift-Off Characteristics and Flame Base Structure of Coal Seeded Gas Jet Flames

An experimental study of the burner rim stability characteristics and the flame base structure of flames co-fired with pulverized coal and propane gas is presented. Lift-off and reattachment characteristics are examined as functions of propane concentration in the jet stream for lignite, bituminous and anthracite coals. The effects on flame base structure are studied in terms of temperature, product species concentration and radiation profiles. The addition of lignite and anthracite coals favours the lift-off transitions. Bituminous coal, on the other hand, makes the flame more stable. The peak values of temperature and concentrations of major combustion product species in the flame stabilization region strongly depend upon the rank of coal. Among the coals tested, bituminous coal produces the highest peak temperature and its flame emits maximum radiation from the stabilization region. Anthracite and lignite coals produce somewhat comparable stability characteristics and structure of the flame base. The effects of coal rank are explained by the differences in volatile matter, moisture and pyrolysis characteristics of coals.
In Situ Measurements of the Photometric Properties of an Area on the Lunar Surface

Photometric properties of lunar surface target areas from high resolution TV pictures received from Surveyor 1 spacecraft
A Novel Half-Cell Design and Fabrication for an In-Situ Evaluation of Pem Fuel Cell Electrocatalysts

A novel electrochemical half-cell is designed and fabricated for in-situ evaluating both anode and cathode catalysts that mimic PEM fuel cell operating conditions. Both carbon-supported Pt and Pt0.5Ru0.5 catalysts are used to prepare the catalyst-coated membrane electrodes for this half-cell validation. A gas feeding system is constructed for quantitatively supplying of H2, H2+CO, or O2 gases to the half-cell for measurements. CO-tolerance of the anode catalyst in hydrogen oxidation reaction (HOR) is tested using this cell. The oxygen reduction reaction (ORR) on Pt/C-coated membrane electrode is studied using this half-cell, further confirming the feasibility of this half-cell design and fabrication. It is expected that this half-cell is also useful for catalyst/catalyst layer evaluation for direct liquid fuel cells.
Bis-phosphatidic acid in developing soybeans and soybean suspension cultures

A phospholipid which rapidly accumulates radioactivity from [1-14C] acetate administered to slices of developing soybeans or to suspension cultures of soybean cells was isolated. Its structure was identified by comparison of its properties and degradation products with those of authentic lipid standards using infrared absorption spectrometry, thin layer chromatography, acetolysis, mild alkaline hydrolysis, and determination of molar ratios of phosphorus, glycerol, and acyl moieties. The structure of the phospholipid was found to bebis-phosphatidic acid, a phospholipid previously unreported in higher plants.
Emerging CAE technologies and their role in Future Ambient Intelligence Environments

Dramatic improvements are on the horizon in Computer Aided Engineering (CAE) and various simulation technologies. The improvements are due, in part, to the developments in a number of leading-edge technologies and their synergistic combinations/convergence. The technologies include ubiquitous, cloud, and petascale computing; ultra high-bandwidth networks, pervasive wireless communication; knowledge based engineering; networked immersive virtual environments and virtual worlds; novel human-computer interfaces; and powerful game engines and facilities. This paper describes the frontiers and emerging simulation technologies, and their role in the future virtual product creation and learning/training environments. The environments will be ambient intelligence environments, incorporating a synergistic combination of novel agent-supported visual simulations (with cognitive learning and understanding abilities); immersive 3D virtual world facilities; development chain management systems and facilities (incorporating a synergistic combination of intelligent engineering and management tools); nontraditional methods; intelligent, multimodal and human-like interfaces; and mobile wireless devices. The Virtual product creation environment will significantly enhance the productivity and will stimulate creativity and innovation in future global virtual collaborative enterprises. The facilities in the learning/training environment will provide timely, engaging, personalized/collaborative and tailored visual learning.
Child Maltreatment: Implications for Developmental Theory and Research

Developmental theories can be affirmed, challenged, and augmented by incorporating knowledge about atypical ontogenesis. Because investigations of human behavior are restricted by difficulties associated with compromising the integrity of the individual’s biological and psychological functioning, it becomes valuable to draw on the potential afforded by ‘experiments of nature’. Examination of individuals with high-risk conditions and psychopathological disorders can provide an entree into the study of system organization, disorganization, and reorganization. In this article, child maltreatment is examined to illustrate the benefit that can be derived from the study of individuals subjected to nonnormative caregiving experiences. The relevance of research on maltreatment to several important aspects of developmental theory is explicated.
Site directed mutagenesis of the β-subunit of the yeast mitochondrial ATPase

Abstract Site directed mutagenesis has been performed on the gene coding for the β-subunit of the yeast mitochondrial F 1 -ATPase. Two different regions were studied. First, the corresponding yeast amino acid, Tyr-344, which was affinity labeled in the bovine enzyme was changed to Phe-344 and Ala-344. The Phe-344 enzyme was completely active and less sensitive to the affinity reagent, 4-chloro-7-nitrobenzofurazan. In contrast, the in vivo level of the Ala-344 enzyme was greatly diminshed and apparently inactive. The second region studied is in the glycine rich region homologous in nucleotide binding proteins. Five different replacements were made and all mutations but one completely eliminated the biological activity and reduced the in vivo level of the mutant peptides. These results support the importance of these amino acids in the function of the ATPase.
Checking the Pulse of Diversity among Health Care Professionals An Analysis of West Coast Hospitals

What factors are associated with variation in the racial/ethnic composition of hospital health care professionals? Institutional theories suggest that organizations react to external environmental and internal structural pressures for the racial/ethnic integration of workers. Using an institutional framework, we bring to bear new insight into how hospitals respond to such pressure for diversity. Models estimated with original data from 328 U.S. West Coast hospitals provide evidence that establishment size and a hospital’s minority patient base promote diversity among health care professionals. The state legal environment is also associated with the racial/ethnic composition of professional hospital workers, indicating the importance of fair employment laws and court decisions in signaling expectations about workplace diversity. Last, the findings show that factors within hospitals’ competitive and internal environments have positive consequences for diversity among health care professionals. We discuss im...
Is Heparin Reversal Required for the Safe Performance of Percutaneous Endovascular Aortic Aneurysm Repair

Background Percutaneous endovascular aneurysm repair (PEVAR) can be performed with high technical success rates and low morbidity rates. Several peer-reviewed papers regarding PEVAR have routinely combined heparin reversal with protamine before sheath removal. The risks of protamine reversal are well documented and include cardiovascular collapse and anaphylaxis. The aim of this study is to review outcomes of patients who underwent PEVAR without heparin reversal. Methods All patients who underwent percutaneous femoral artery closure after PEVAR between 2009–2012 without heparin reversal were reviewed. Only patients who underwent placement of large-bore (12- to 24-French) sheaths were included. Patient demographics, comorbidities, operative details, and complications were reported. Results One hundred thirty-one common femoral arteries were repaired using the Preclose technique in 76 patients. Fifty-five patients underwent bilateral repair and 21 underwent unilateral repair. The mean age was 73.9 ± 9.1 years. The mean heparin dose administered was 79 ± 25.4 U/kg. The mean patient body mass index was 27.5 ± 4.8 kg/m 2 . Ultrasound-guided arterial puncture was performed in all patients. Average operative times were 196.5 ± 103.3 min, and the mean estimated blood loss was 277.6 mL. Four femoral arteries (3%) required open surgical repair after failed hemostasis with ProGlide closure (Abbott Vascular, Abbott Park, IL). Two patients required deployment of a third ProGlide device with successful closure. Two patients had small ( Conclusions PEVAR may be performed with low patient morbidity after therapeutic heparinization without heparin reversal. Femoral artery repair after the removal of large-diameter sheaths using the Preclose technique can be performed in this setting with minimal rates of early and late bleeding or thrombosis.
Allogeneic Transplantation for MDS/AML Patients with Germline GATA2 Mutations

Days to ANC 28 151 23 1560 0.31 Days to PLT Engraft 45 25-81 42 14105 0.93 Days to Chimerism 28 1997 29 13100 0.67 N[ % N[ % Alive, Died 17, 14 54.8, 45.2 67, 47 58.8, 41.2 0.69 Relapse 1 of 31 4.8 16 of 64 21.6 0.11 aGVHD 11 35.5 55 48.2 0.23 cGVHD 2 6.4 6 5.3 0.68 ANC Engraft 20 64.5 82 71.9 0.51 PLT Engraft 17 54.8 79 69.3 0.14 Chimerism >95% 15 48.4 79 69.3 0.031 TRM 12 38.7 20 17.5 0.012
210Pb/226Ra and 210Po/210Pb disequilibria in seawater and suspended particulate matter

Abstract The distribution of 210 Po and 210 Po in dissolved ( 0.4 μm) phases has been measured at ten stations in the tropical and eastern North Atlantic and at two stations in the Pacific. Both radionuclides occur principally in the dissolved phase. Unsupported 210 Pb activities, maintained by flux from the atmosphere, are present in the surface mixed layer and penetrate into the thermocline to depths of about 500 m. Dissolved 210 Po is ordinarily present in the mixed layer at less than equilibrium concentrations, suggesting rapid biological removal of this nuclide. Particulate matter is enriched in 210 Po, with 210 Po/ 210 Pb activity ratios greater than 1.0, similar to those reported for phytoplankton. Box-model calculations yield a 2.5-year residence time for 210 Pb and a 0.6-year residence time for 210 Po in the mixed layer. These residence times are considerably longer than the time calculated for turnover of particles in the mixed layer (about 0.1 year). At depths of 100–300 m, 210 Po maxima occur and unsupported 210 Po is frequently present. Calculations indicate that at least 50% of the 210 Po removed from the mixed layer is recycled within the thermocline. Similar calculations for 210 Pb suggest much lower recycling efficiencies. Comparison of the 210 Pb distribution with the reported distribution of 226 Ra at nearby GEOSECS stations has confirmed the widespread existence of a 210 Pb/ 226 Ra disequilibrium in the deep sea. Vertical profiles of particulate 210 Pb were used to test the hypothesis that 210 Pb is removed from deep water by in-situ scavenging. With the exception of one profile taken near the Mid-Atlantic Ridge, significant vertical gradients in particulate 210 Pb concentration were not observed, and it is necessary to invoke exceptionally high particle sinking velocities to account for the inferred 210 Pb flux. It is proposed instead that an additional sink for 210 Pb in the deep sea must be sought. Estimates of the dissolved 210 Pb/ 226 Ra activity ratio at depths greater than 1000 m range from 0.2 to 0.8 and reveal a systematic increase, in both vertical and horizontal directions, with increasing distance from the sea floor. This observation implies rapid scavenging of 210 Pb at the sediment-water interface and is consistent with a horizontal eddy diffusivity of 3−6 × 10 7 cm 2 /sec. The more reactive element Po, on the other hand, shows evidence of rapid in-situ scavenging. In filtered seawater, 210 Po is deficient, on the average, by ca. 10% relative to 210 Pb; a corresponding enrichment is found in the particulate phase. Total inventories of 210 Pb and 210 Po over the entire water column, however, show no significant departure from secular equilibrium.