cssi/SciSciGPT-SciSciNet huggingface dataset:
Two Cycles of High Dose Chemotherapy with Autologous Bone Marrow Support for Patients with Locally Advanced Breast Cancer

: Purpose: To examine the impact of two cycles of high dose chemotherapy (HDC) with autologous bone marrow rescue (ABMR) in the treatment of women with locally advanced breast cancer. Patients and Methods: Twenty-three patients not exhibiting progressive disease to conventional dose therapy (ltx) were eligible for HDC. Conventional dose regimens used were the CAMFTP regimen (n= 6), 5-FU, doxorubicin and cyclophosphamide (n= 3), cyclophosphamide, methotrexate and 5-FU (n= 1), or doxorubicin/cyclophosphamide (n= 13). HDC on each cycle consisted of etoposide 625 mg/m2, cyclophosphamide 6 gr/m2, carboplatin 2 gr/m2 with ABMR. Median age of the patients was 40 years. Results: Seventeen patients (74%) underwent two cycles of HDC; 6 received only one cycle due to insurance refusal to pay for C2 (1), toxicity from C1 (4), death on C1(1). There were 2 transplant-related deaths due to fungal infections 1 each on C1 and C2. Four patients achieved complete remission (CR) with Itx, 18 achieved partial remission (PR), and 1 had stable disease (SD). One patient was converted from PR to CR with HDC. There are 9/23 (39%) patients alive and progression-free with median follow-up of 27 months. (range 21-41 + months). Twelve of the 23 (52%) have progressed at a median of 7 months (range 4-32) from bone marrow transplant (BMT) and there were 2 early deaths (9%). Six patients received only one cycle of HDC and 2 of these are alive and progression-free at 36 and 38 months of follow-up. Of the 17 completing two cycles of HDC, 7/17 (41%) are alive and progression-free with follow-up of 21-41 months. The median progression-free survival (PFS) for the entire group is 13 months and median overall survival is 21 months (range 1–41 + mos). Conclusion: Despite the use of two cycles of HDC with ABMR, systemic relapse remains the major obstacle to cure in women with locally advanced breast cancer; there is a need to develop more effective preparative rgimens.
Electron-positron scattering resonances from relativistic two-body wave equations

Abstract The K -matrix for electron-positron scattering is evaluated in the 0 + channel for each of three relativistic wave equations derived from QED. When all the transverse single-photon-exchange contributions are treated we obtain zero width resonances or continuum bound states at mass values of 1.351, 1.498, 1.659, 1.830, 2.009, and 2.195 MeV. We assume that neglected processes are not crucial to the complete problem and therefore we compare these results with electron-positron coincidence peaks found in heavy ion experiments performed at GSI. We suggest additional types of experiments to search for these resonances.
TU-B-342-01: SPECT/CT and PET/CT Dosimetry

This presentation will discuss the dosimetric factors associated with PET/CT and SPECT/CT including those associated with the administration of radiopharmaceuticals for both PET and SPECT and the specific factors associated application of CT in these hybrid modalities. The dosimetry of the application of these modalities to pediatrics will also be discussed. For SPECT, the dosimetry of the administration of radiopharmaceuticals typically used in SPECT as well as potential methods for maintaining these doses at reasonably low levels. In particular, myocardial perfusion imaging will be discussed. Also the use of new reconstruction techniques and how they may be used to lower the administered activity for some SPECT applications will be discussed. For PET, the dosimetry associated with the use of 18 F fluoro‐deoxy‐glucose (FDG) will be discussed including different technical approaches that may lead to lower administered activity. Lastly, the application of CT to both SPECT and PET will be discussed including the requirements for CT‐based attenuation correlation, anatomical correlation and diagnostic CT. Potential methods to reduce CT dose in these protocols will be discussed. Educational Objectives: 1. Discuss 2 potential ways to reduce the administered activity in SPECT. 2. Describe 2 ways that the acquisition of PET can be modified to make it more efficient. 3. List 3 approaches that can be used to reduce the dose of the CT used in conjunction with PET and SPECT.
Sensor topologies for application of strain energy damage diagnostics and prognostication

Structural health monitoring methodologies devised over the past two decades have increasing shown improved robustness in capability to identify the onset of structural damage and locate the source of the damage. However, the pathway to prognostication and life-cycle assessment through structural health monitoring remains stalled by a lack of success in the diagnostic step of experimentally quantifying the severity of damage in suitable, engineering quantities. Of the methods devised, strain energy approaches have demonstrated not only strength in identifying and localizing structural damage but also uniquely provide a theoretical basis for quantifying damage through measurement of relative stiffness loss in individual members. Conventional applications of strain energy methods use distributed accelerometers, often being single-axis and oriented in the same direction. The limited degrees-of-freedom measured limits the modal parameter extraction to a reduced subset and yields only partial reconstruction of the strain energy in the system. Furthermore, it has been shown experimentally and proven analytically that improvement in strain energy methods through increased spatial density of the sampling array is constrained by the effect of measurement noise on the accuracy of the numerical computations. In this paper, alternative sensor topologies are explored for improving the reconstruction of strain energy estimates. An experimental component of the research includes strain energy estimates for a fixed-free beam heavily instrumented with accelerometers. Prescribed damage is incrementally applied to the beam to permit a basis for comparison amongst the sensor topologies in addressing the damage diagnostics problem with specific emphasis on quantification of severity through stiffness loss.
Simultaneous multifrequency observations of Jovian S bursts

The millisecond component of the Jovian decameter emission was studied at high resolution in order to examine the short-term behavior of the S-burst drift rates and to define the drift rate spectrum at high frequencies. By using dynamic spectra of 300 microsec and 3.3 kHz resolution and covering discrete frequency bands in the 26-33 MHz range, large systematic changes in the magnitude of the S-burst drift rates are observed on a time scale of seconds to minutes. The drift rate variability, its dependence on frequency, and absence of the predicted drift rate turnover in the spectrum are interpreted in terms of an ionospheric electron source. Low-resolution intensity-time tracings, abrupt changes in mean drift rates from group to group, and systematic variations in the group-to-group mean drift rates due to predictable temporal changes in the magnetic field gradient on the Io flux tube are discussed. These temporal changes are due to motion of the Io-associated magnetic flux tube in the Jovian magnetosphere.
Accuracy of the Houston approximation for electron motion in a lattice and an electric field

The accuracy of the Houston approximation for the wave function of an electron in a perfectly periodic lattice and an applied uniform d.c. electric field is investigated. It is shown that the Houston function is not a good approximate solution to Schrodinger's equation since it leads to inconsistent results both for the velocity and the acceleration of the electron wave. Just how serious this error can be is illustrated graphically using the Kronig-Penney model as an example.
Distribution patterns of membrane-bound and soluble enzymes in mitochondrial populations.

Abstract Mitochondria were isolated from normal rat liver, kidney, and heart, and from mouse liver and ascites tumor cells, and were dispersed through linear sucrose density gradients in a zonal centrifuge. Distributions of the enzyme activity with respect to mean particle size were constructed. The medians of the distributions for the activities of several enzymes associated with the membranes were significantly different from the medians of the distributions of the soluble mitochondrial enzymes when the mean particle diameters of the fractions were used as the measure of particulate size. On the other hand, when the activity of an outer-membrane enzyme was determined as a function of the area of the mitochondria and the activities of the soluble enzymes were expressed as a function of the volume, the calculated particle diameters corresponding to the respective midpoints of these distributions were in better agreement. This congruence suggests that mitochondria are more nearly homogeneous with respect to the enzyme activities examined than previously proposed. Furthermore, since the distribution of the inner membrane activities was similar to those of the outer membrane enzymes, the area of the inner membrane may be proportional, not to the volume of the mitochondria, but to the area of the outer membrane.
Estimation of the critical surface tension of wetting of hydrophobic solids by flotation

Abstract A method for the estimation of the critical surface tension of wetting of solids (γ c ) is demonstrated using MoS 2 , S o , oil shale, teflon, and MoS 2 -SiO 2 mixtures ground together. The method consists of obtaining percent recovery (%r) versus liquid surface-tension (γ LV ) plots and extrapolating the curve to %r = 0. Good correlation between the method of Zisman using contact-angle measurements and the present flotation technique were established. γ c values for MoS 2 , S o , and teflon were found to be 26, 31.5 and 20.5 dyn cm −1 , respectively. The γ c of oil shale depended on its organic-carbon content. It was also observed that although SiO 2 ground together with MoS 2 is only partly covered with specs of the latter mineral, the γ c of the new composite material obtained approaches that of HoS 2 .
Condylar trauma and facial asymmetry: an experimental study.

Summary Surgical intracapsular condylar fractures were initiated on young monkeys followed by prolonged intermaxillary fixation in an effort to create facial asymmetry and induce temporomandibular joint ankylosis. Implanted head positioners and metallic bone markers were used to document developing facial asymmetry in all animals. Vertical opening capabilities were fully recovered and the procedures had no discernible functional impact. Slight limitation of movement persisted only in the translation of the damaged condyles. It was concluded that trauma followed by long term fixation had no effect in promoting ankylosis or significant limitation of jaw movement. It is suggested that when considering the role of trauma in the aetiology of ankylosis, attention be given to those factors which may complicate an existing trauma.
The advantages of physiotherapy for burn patients under anaesthesia

Abstract In 34 burn patients, with limitation of joint function and requiring anaesthesia for surgical procedures, 15 different joints and a total of 110 joints were put through a range of motion exercises before, during and after narcosis. A weighted average improvement of 46 per cent of normal range of motion was attained during anaesthesia, and most of this improvement was retained thereafter. Gentle, passive stretching exercises during anaesthesia are recommended to improve limited joint motion due to burns.
The effect of variation in molecular weight on the antigenicity of dextran in man.

Abstract The capacity of a series of dextran fractions of graded molecular weight to stimulate antibody formation in man upon injection of 1 mg. dextran was investigated. A significant drop in capacity to elicit antibody formation was found with dextran fractions of average molecular weight of 51,300 or below. The precipitating antibodies to the dextran fractions were generally similar to those produced to native dextran as determined by quantitative precipitin and oligosaccharide inhibition studies. Wheal and erythema reactions to the dextran fractions were obtained when circulating precipitin levels were above 7–8 μg. antibody N/ml.
Epitaxial deposition of GaInN and InN using the rotating susceptor ALE system

The growth of GaInN ternary alloys has been investigated using atomic layer epitaxy. Single crystal films have been deposited at 100 Torr in the 600°C to 700°C temperature range using the rotating susceptor approach. The InN percentage in the deposited films were found to depend on more than just the gas phase In/Ga ratio. In addition to the relative indium to gallium composition of the precursor gases, the indium incorporation was also found to depend on the absolute partial pressures of the reactant gases. The indium incorporation increases with decreasing growth temperatures, and may reach a temperature dependent saturation limit for a given set of growth conditions. Optimization of the ALE growth process has resulted in single crystal films exhibiting band edge room temperature photoluminescence for InN percentages of up to 27% in the GaInN ternary films. In addition, single crystal indium nitride has been grown using the ALE technique at 480°C.
The role of the VPS4A-exosome pathway in the intrinsic egress route of a DNA-binding anticancer drug.

This study investigates the subcellular pharmacokinetics of drug efflux in cancer cells and explores the role of the multivesicular body (MVB) in facilitating efflux of doxorubicin, a widely used DNA-targeting anticancer agent, from the nucleus. Human erythroleukemic K562 cells were pulsed with doxorubicin and then chased in drug-free media to allow for efflux. Microscopy and biochemical techniques were used to visualize the subcellular localization of the drug and measure drug content and distribution during the efflux period. To explore the role of the MVB in doxorubicin efflux, K562 cells were transfected with dominant negative mutant forms of VPS4a–GFP chimeras. Although the intracellular concentration of drug exceeds the extracellular concentration, nuclear efflux of doxorubicin occurs in living cells at a faster rate than doxorubicin unbinding from isolated nuclei into drug-free buffer. In cells expressing dominant negative VPS4a, doxorubicin accumulates in VPS4a-positive vesicles and drug sequestration is inhibited, directly implicating the MVB pathway in the egress route of doxorubicin in this cell type. Cellular membranes are a component of the doxorubicin efflux mechanism in K562 cells. Dominant-negative GFP chimeric mutants can be used to elucidate the role of specific membrane trafficking pathways in subcellular drug transport routes.
Effect of α-tocopherol and Trolox on the decomposition of methyl linoleate hydroperoxides

To clarify the mechanisms of antioxidant action, the effect of α-tocopherol and its water-soluble carboxylic acid derivative, Trolox, was studied on the decomposition of methyl linoleate hydroperoxides (MeLoOOH). Decomposition rate and the distribution of autoxidation products formed from MeLoOOH were followed by analyzing the volatile and nonvolatile products by static headspace gas chromatography and normal-phase high-performance liquid chromatography, respectively. Both α-tocopherol and Trolox markedly inhibited the decomposition of MeLoOOH in a concentration-dependent way. In the absence of antioxidants, MeLoOOH was completely decomposed after incubation for 48 h at 60°C, and in the presence of equal molar concentration of antioxidants only 6–7% of initial MeLoOOH was decomposed even after 280 h of incubation. MeLoOOH produced 1.2% methyl linoleate hydroxy compounds (MeLoOH) in the presence of α-tocopherol and 3.8% in the presence of Trolox. Both antioxidants inhibited the formation of volatile decomposition products and the formation of ketodiene compounds. The hydroxy compounds may be formed by the reaction of alkoxy radical and hydrogen donating antioxidants. Conversion of MeLoOOH into stable MeLoOH demonstrated that the antioxidants α-tocopherol and Trolox trap alkoxyl radicals by H-donation.
The influence of the bone-implant interface stiffness on stress profiles surrounding Al2O3 and carbon dental implants

Dental implants have been used and studied for the replacement of missing teeth for many years. Finite element stress analysis (FESA) has previously been used in their evaluation to study the effect of various design parameters on induced stresses. A two-dimensional FESA was used to evaluate the effect that the implant-bone interface elastic modulus has on the stress distribution around LTI carbon and aluminum oxide dental implants. The results of this investigation indicate that a soft tissue interface between implants and bone negates the effect of implant elastic modulus and results in stress profiles that were almost identical for the LTI carbon and aluminum oxide implants.
Urea and guanidine hydrochloride induced dissociation and denaturation of bacteriophage F2 capsid.

A single, low molecular weight protein is found after urea or guanidine hydrochloride (Gdn.HCl) treatment of empty capsids derived from bacteriophage f2. The final product of denaturation is apparently a monomer, existing as a random coil in larger than or equal to 4.0 M Gdn.HCl but in a less extended form in 8.0 M urea. In contrast, an 11 S protein component is isolated after treatment of the intact virus with 4.0 M Gdn.HCl (Zelazo & Haschemeyer, 1969), indicating that RNA plays a role in stabilizing larger subunits. Denaturation by Gdn.HCl occurs in two stages as measured by changes in CD and Stokes radius: dissociation that involves a structural perturbation of aromatic side chains, followed by a major, cooperative transition that evidently results in the loss of all noncovalent structure. Denaturation by urea appears to be a much less cooperative process that occurs in several steps over a wide range of urea concentration (1--7 M). In both urea and Gdn.HCl, dissociation into subunits begins at a lower concentration of denaturant than the major changes in conformation.
Selective primary health care: Old wine in new bottles

This paper comments on a previous paper on selective primary health care (PHC) written by Drs. Walsh and Warren. The PHC approach as developed under the guidance of the World Health Organization (WHO) represents the key health services/sector component of the basic needs strategy. This author finds that the lack of analytical rigor in the critical paper is a serious flaw. Another criticism is levelled against them with regard to established priorities for health care. In discussing "feasibility of control" the meaning implied is the technical possibility of controlling a disease through vaccine spraying or chemotherapy. To a health planner this appears quite differently. A vaccine is insignificant if the health care network is not in contact with the masses. Resource availability (finances trained workers etc.) and allocation are the context in which all of this must be considered. Once the diseases to be treated and prevented have been selected the next step is to devise interventions of reasonable cost and practicability. This does not take into account true considerations for those factors. Comprehensive PHC as understood by Walsh and Warren is probably not going to be available for everyone in the near future. However by implying that basic PHC systems are beyond the reach of low income countries is an error. Selective PHC is the authors maintain potentially the most cost-effective type of medical intervention and the authors recommend a mix of health care activities. This proposal is different in that it provides services for a certain group within the population (young children up to age 3 and women of childbearing age) while preventing or denying others. This in itself would be quite difficult to accomplish. This author maintains that it is virtually impossible to conceive of circumstances which would justify a fixed unit carrying out only a very narrow range of activities as proposed by Walsh and Warren. Clearly the authors are correct when they observe that flexibility is necessary; that certain types of care and treatment should be added when they become available or subtracted when they are not longer needed. The existing health care infrastructure which already exists in most countries is being ignored as is the possibility of its great expansion in this decade. Nor does the original paper address the nature of the wider development process. The priority activities advocated by Drs. Walsh and Warren are quite compatible; with the balanced set of PHC development; these may be essential for the successful extension of these high priority activities to the mass of low income country populations.
Kit and FcϵRI mediate unique and convergent signals for release of inflammatory mediators from human mast cells

In human mast cells, derived from CD34(+) peripheral blood cells, we observed that Kit ligand (KL) failed to induce degranulation but acted in synergy with antigen to markedly enhance degranulation, levels of cytokine gene transcripts, and production of cytokines. Further examination revealed that antigen and KL activated common and unique signaling pathways to account for these varied responses. KL, unlike antigen, failed to activate protein kinase C but activated phospholipase Cgamma and calcium mobilization and augmented these signals as well as degranulation when added together with antigen. Both KL and antigen induced signals that are associated with cytokine production, namely phosphorylation of the mitogen-activated protein kinases, phosphatidylinositol 3-kinase-dependent phosphorylation of protein kinase B (also known as Akt), and phosphorylation of nuclear factor kappaB (NFkappaB). However, only KL stimulated phosphorylation of signal transducer and activator of transcription 5 (STAT5) and STAT6, whereas antigen weakly stimulated the protein kinase C-dependent induction and phosphorylation of c-Jun and associated activating protein-1 (AP-1) components, an action that was markedly potentiated by costimulation with KL. Interestingly, most signals were down-regulated on continuous exposure to KL but were reactivated along with cytokine gene transcription on addition of antigen. The findings, in total, indicated that a combination of FcepsilonRI and Kit-mediated signals and transcriptional processes were required for optimal physiologic responses of human mast cells to antigen.
A simple and improved correction for population stratification in case-control studies.

Population stratification remains an important issue in case-control studies of disease-marker association, even within populations considered to be genetically homogeneous. Campbell et al. (Nature Genetics 2005;37:868–872) illustrated this by showing that stratification induced a spurious association between the lactase gene (LCT) and tall/short status in a European American sample. Furthermore, existing approaches for controlling stratification by use of substructure-informative loci (e.g., genomic control, structured association, and principal components) could not resolve this confounding. To address this problem, we propose a simple two-step procedure. In the first step, we model the odds of disease, given data on substructure-informative loci (excluding the test locus). For each participant, we use this model to calculate a stratification score, which is that participant’s estimated odds of disease calculated using his or her substructure-informative–loci data in the disease-odds model. In the second step, we assign subjects to strata defined by stratification score and then test for association between the disease and the test locus within these strata. The resulting association test is valid even in the presence of population stratification. Our approach is computationally simple and less model dependent than are existing approaches for controlling stratification. To illustrate these properties, we apply our approach to the data from Campbell et al. and find no association between the LCT locus and tall/short status. Using simulated data, we show that our approach yields a more appropriate correction for stratification than does principal components or genomic control.
VERIFY: a program for proving correctness of digital hardware designs

Abstract verify is a prolog program that attempts to prove the correctness of a digital design. It does so by showing that the behavior inferred from the interconnection of its parts and their behaviors is equivalent to the specified behavior. It has successfully verified large designs involving many thousands of transistors.
Vision-based guidance for an automated roving vehicle

A controller designed to guide an automated vehicle to a specified target without external intervention is described. The intended application is to the requirements of planetary exploration, where substantial autonomy is required because of the prohibitive time lags associated with closed-loop ground control. The guidance algorithm consists of a set of piecewise-linear control laws for velocity and steering commands, and is executable in real time with fixed-point arithmetic. The use of a previously-reported object tracking algorithm for the vision system to provide position feedback data is described. Test results of the control system on a breadboard rover at the Jet Propulsion Laboratory are included.
Quality Assurance in Medicine

The authors describe and reflect on current activities in the field, and focus on three initiatives in quality assurance sponsored by the federal government.
Infrared (10.6-μm) scattering and extinction in laboratory water and ice clouds

Measurements of the angular scattering and extinction of IR (10.6-μm) laser radiation in laboratory water and ice clouds are reported and compared to theoretical predictions for spheres and visible (0.633-μm) light scattering data. Randomly oriented cloud particles with dimensions ranging from several times smaller to larger than the incident wavelength generated phase functions span the Rayleigh and Mie scattering domains and illustrate the effects caused by strong internal energy absorption. Dual-wavelength extinction measurements reveal information on the growth and dissipation of laboratory water clouds and the effects of cloud seeding. The remote sensing significance of the findings is discussed.
Optimizing process time for utrafiltration and diafiltration

Abstract Models have been derived to predict process time and permeate volume for the purification of a macromolecule by ultrafiltration (in the concentration mode) or by continuous diafiltration. It requires only knowledge of the parameters of the film theory (gel-polarization) model for flux. Purification by discontinuous diafiltration usually results in less time and generates lower permeate volume than continuous diafiltration alone. The optimum appears to be a combined process where the feed is first pre-concentrated by ultrafiltration, followed by continuous diafiltration.
The CDF trigger

Abstract The trigger for the Collider Detector at Fermilab (CDF) is described. The detector is designed to study 2 TeV p p collisions at a luminosity of 10 30 cm −2 s −1 . The interaction rate of 50 kHz is reduced by the trigger to the full event readout rate of 1–100 Hz.
Asymptotic behaviour of the solutions of a nonlinear difference equation

We study the following nonlinear difference equation: where the coefficients E n are non-negative and lim sup E n < 1. In the special case of periodic coefficients, it was conjectured by Ladas that every positive solution of this equation is periodic with period 2 and this conjecture was proved by Chen. In this paper, we allow the coefficients E n to be non-periodic and prove that every positive solutions converges to a period 2 solution. We also generalize Chen's result by providing a more general sufficient condition for the eventual periodicity of all positive solutions of this equation.
Amino Acid Racemization in Pseudomonas putida KT2440

d-Amino acids have been shown to play an increasingly diverse role in bacterial physiology, yet much remains to be learned about their synthesis and catabolism. Here we used the model soil- and rhizosphere-dwelling organism Pseudomonas putida KT2440 to elaborate on the genomics and enzymology of d-amino acid metabolism. P. putida KT2440 catabolized the d-stereoisomers of lysine, phenylalanine, arginine, alanine, and hydroxyproline as the sole carbon and nitrogen sources. With the exception of phenylalanine, each of these amino acids was racemized by P. putida KT2440 enzymes. Three amino acid racemases were identified from a genomic screen, and the enzymes were further characterized in vitro. The putative biosynthetic alanine racemase Alr showed broad substrate specificity, exhibiting measurable racemase activity with 9 of the 19 chiral amino acids. Among these amino acids, activity was the highest with lysine, and the kcat/Km values with l- and d-lysine were 3 orders of magnitude greater than the kcat/Km values with l- and d-alanine. Conversely, the putative catabolic alanine racemase DadX showed narrow substrate specificity, clearly preferring only the alanine stereoisomers as the substrates. However, DadX did show 6- and 9-fold higher kcat/Km values than Alr with l- and d-alanine, respectively. The annotated proline racemase ProR of P. putida KT2440 showed negligible activity with either stereoisomer of the 19 chiral amino acids but exhibited strong epimerization activity with hydroxyproline as the substrate. Comparative genomic analysis revealed differences among pseudomonads with respect to alanine racemase genes that may point to different roles for these genes among closely related species.
Life's a game and the game of life: how making a game out of it can change student behavior

There is little argument that creating experiences for students that will increase student success and retention is a goal that is shared by anyone teaching courses. In computing courses, we have seen a lot of focused attention on the first year introductory courses as it has been shown that it is failure in these courses that drives students away from the discipline. In this paper we describe success we have had with first year students through the creation of achievement system for the undergraduate experience. Through the Just Press Play project and its associated achievements, we observed a significant shift in student behavior in relation to our first year students which lead to a greater level of student success in their first course.
LACK OF RELATIONSHIP BETWEEN HYPOGLYCEMIC AWARENESS AND CATECHOLAMINE (CAT) RESPONSE IN INSULIN DEPENDENT DIABETES (IDD)

We assessed hypoglycemic symptoms in 29 children aged 15.4±2.4 yrs (x±SD) with IDD duration 7.9±3.7 yrs. without clinical evidence of autonomic neuropathy. An intravenous insulin bolus of 0.15-0.75 u/kg according to basal plasma glucose (PG) was given before and again after 3 days of intensive insulin therapy (IIT). Oral questionnaires regarding hypoglycemic symptoms were completed at each time blood samples were taken for measurements of PG and CATS. A hypoglycemic awareness score (HAS) was assigned to each patient. All but one patient reported symptoms during each test. These occurred prior to hypoglycemia (PG>65 mg%) in 73% before and 52% after IIT. The initial symptoms (usually hunger) appeared at 38±26 min. before and 35±18 min. after IIT after PG decrements of 121±81 (47±28%) and 88±64 mg% (46±26%) resp. (NS). The CAT increments at this time were very small (174±55, range 0-802 and 70±89, 0-262 pg/ml resp.). The maximum HAS correlated negatively with PG nadir, before (r=-.69, p 250 pg/ml. Thus hypoglycemic unawareness is not common in children with IDD and symptoms occur prior to the onset of hypoglycemia with minimal if any CAT increments.
Regionally-specific microglial activation in young mice over-expressing human wildtype alpha-synuclein

Parkinson's disease (PD) is characterized by widespread alpha-synuclein pathology and neuronal loss, primarily of the nigrostriatal dopaminergic neurons. Inflammation has been implicated in PD, and alpha-synuclein can initiate microglial activation; however, the kinetics and distribution of inflammatory responses to alpha-synuclein overexpression in vivo are not well understood. We have examined the regional and temporal pattern of microglial activation and pro-inflammatory cytokine production in mice over-expressing wild-type human alpha-synuclein driven by the Thy1-promoter (Thy1-aSyn mice). An increased number of activated microglia, and increased levels of TNF-α mRNA and protein were first detected in the striatum (1 month of age) and later in the substantia nigra (5-6 months), but not the cerebral cortex or cerebellum; in contrast, IL-1β and TGF-β remained unchanged in the striatum and substantia nigra at all ages examined. Microglial activation persisted up to 14 months of age in these regions and only minimal increases were observed in other regions at this later age. Increased concentrations of serum TNF-α were observed at 5-6 months, but not at 1 month of age. The expression of toll-like receptors (TLRs) 1, TLR 4 and TLR 8, which are possible mediators of microglial activation, was increased at 5-6 months in the substantia nigra but not in the cerebral cortex, and TLR 2 was increased in the substantia nigra at 14 months of age. With the exception of a slight increase in the striatum of 14 month old Thy1-aSyn mice, MHCII staining was not detected in the regions and ages examined. Similarly, peripheral CD4 and CD8-postive T cells were increased in the blood but only at 22 months of age, suggesting later involvement of the adaptive immune response. These data indicate that, despite the presence of high levels of alpha-synuclein in other brain regions, alpha-synuclein overexpression caused a selective early inflammatory response in regions containing the axon terminals and cell bodies of the nigrostriatal pathway. Our results suggest that specific factors, possibly involving a regionally and temporally selective increase in TLRs, mediate alpha-synuclein-induced inflammatory responses in the SN, and may play a role in the selective vulnerability of nigrostriatal dopaminergic neurons in PD.
A monoclinic crystal form of casein kinase 1 δ

Casein kinase 1 δ (CK1δ) is a regulatory enzyme in the mammalian circadian oscillator and represents a potential pharmacological target for modulating circadian rhythms. Crystal structures of four different polymorphs of CK1δ have previously been determined and this article reports the crystallization and structure determination of a new crystal form belonging to space group P21. Comparison of CK1δ crystal structures reveals few conformational differences within the C-terminal lobe, but more significant movements of the β-sheet region of the N-terminal lobe were observed.
Host−Guest Complexation in Self-Assembled Monolayers: Inclusion of a Monolayer-Anchored Cationic Ferrocene-Based Guest by Cyclodextrin Hosts

A novel ferrocenyl disulfide of the type ω,ω‘-dithiobis[alkyl(dimethyl)(ferrocenylmethyl)ammonium bromide] was synthesized and coassembled with nonanethiol on vapor deposited Au(111) electrode surfaces. The coassembled ferrocene-based cationic guest monolayer assembly was found to bind with β- and γ-cyclodextrins to form stable host−guest complexes. The cyclodextrin hosts are believed to interact with the monolayer assembly in two ways: by inclusion of the ferrocene moiety within the cyclodextrin cavity and by interactions between the counterions (e.g., Br-, PF6-, or ClO4-) and the hydrophilic planes of the cyclodextrin molecules. Interactions between the monolayer and cyclodextrin are manifested primarily by a decrease in the voltammetric oxidation current for the surface-bound ferrocenyl redox centers after exposure to dilute solutions (e.g., 10 μM) of the cyclodextrin hosts. This decrease in electrochemical activity stems from the restricted access of charge-compensating anions to the ferrocenyl redox...
Patients with congestive heart failure treated by physicians using intravenous nitroglycerin boluses in the emergency department have shorter hospital length of stay

Study objectives: Several studies have shown that high-dose nitroglycerin (NTG) is effective in decreasing the incidence of death, myocardial infarction, and need for mechanical ventilation in patients with congestive heart failure (CHF). We postulate that the use of intravenous NTG boluses in the emergency department (ED) would lead to decreased hospital length of stay for patients with CHF. Methods: This was a retrospective cohort in an urban nonteaching hospital with 43,000 annual ED visits. Consecutive patients treated by emergency physicians during a 20-month period who arrived between midnight and 8 am and were admitted for CHF exacerbation were included. We previously had shown that those arriving between midnight and 8 am were more likely to benefit from aggressive NTG therapy in the ED than those arriving at other times. To lessen the influence of outliers on the results, we a priori excluded patients with a length of stay greater than 10 days. On the basis of responses to a structured survey on the treatment of CHF in the ED, we divided emergency physicians into 2 groups: users and nonusers of intravenous bolus NTG. We then assigned CHF patients to 1 of the 2 groups according to their emergency physician categorization and calculated length of stay for each group of patients. We used Student's t test to compare means (α≤.05 taken as statistically significant). Results: The user and nonuser groups had 19 and 105 patients, respectively. The mean age (66±14 and 71±13 years, respectively) and the percentage of female patients (58% and 50%, respectively) was similar between the groups. The mean length of stay for the user and nonuser groups was 3.7±1.5 and 4.6±2.4 days, respectively. The difference of 0.9 days was statistically significant (95% confidence interval 0.0 to 1.7 days, P =.05). Conclusion: CHF patients who arrive between midnight and 8 am spend almost 1 day fewer in the hospital if they are treated by emergency physicians who use intravenous NTG boluses than if they are treated by those who do not.
Implicitly balanced solution of the two-phase flow equations coupled to nonlinear heat conduction

This paper presents the solution of the two-phase flow equations coupled to nonlinear heat conduction using the Jacobian-free Newton-Krylov (JFNK) method which employs a physics-based preconditioner. Computer simulations will demonstrate that the implicitly balanced solution obtained from the JFNK method is more accurate than traditional approaches that employ operator splitting and linearizing. Results will also indicate that by employing a physics-based preconditioner the implicitly balanced solution can provide a more accurate solution for the same amount of computer time compared to the traditional approach for solving these equations. Finally, convergence plots will show that as the transient time lengthens, the implicitly balanced solution can maintain this higher level of accuracy at much larger time steps.
Effects of regional amygdaloid lesions on flight and defensive behaviors of wild black rats (Rattus rattus)

Flight and defensive behaviors of wild black rats (R. rattus) in response to nonpainful threatening stimuli were examined before and after regional amygdaloid lesions. Striking disruption of flight was found following damage to all major amygdaloid regions. In contrast, reduced defensiveness was most consistently associated with damage to cortical and, perhaps, central nuclei. The diffuse organization of flight behavior may result from extensive modality-specific cortical afferents to the amygdala and the varied provided by naturalistics threats. The more restricted representation of defensive attack may have resulted from diminished responsiveness to vibrissal stimulation mediated by medial and dorsomedial amygdaloid structures.
Growth and Respiration Patterns of Snap Bean Fruits

The relationship of respiration and growth of seed, pericarp tissue and whole fruit of snap beans (Phaseolus vulgaris L.) was studied. The whole fruit exhibited an apparent climacteric type of respiration pattern. This pattern resulted from an increase in CO2 production by the enlarging seed followed by a rapid decrease in CO2 evolution by the pericarp tissue, and the pattern was not associated with any concomitant increase in ethylene production. Therefore, the apparent climacteric respiration pattern of a developing bean fruit is not comparable to the phenomenon that occurs in other ripening fruits.
Assessment of intravenous adipose-derived allogeneic mesenchymal stem cells for the treatment of feline chronic kidney disease: a randomized, placebo-controlled clinical trial in eight cats

ObjectivesFeline chronic kidney disease (CKD) is characterized by chronic tubulointerstitial nephritis, and inflammation contributes to the progression of renal fibrosis. Mesenchymal stem cells (MSCs) have demonstrated anti-inflammatory and antifibrotic effects in rodent CKD models. However, few randomized trials evaluating the effectiveness of MSC therapy for diseases in companion animals have been reported. The purpose of this study was to evaluate the effectiveness of allogeneic MSCs for the treatment of feline CKD using a randomized, placebo-controlled trial.MethodsMSCs were isolated from the cryopreserved adipose tissues of specific pathogen-free research cats and culture expanded. CKD cats were enrolled in a randomized, placebo-controlled, blinded one-way crossover clinical study. Four CKD cats were randomized to receive 2 × 106 MSCs/kg intravenously at 2, 4 and 6 weeks. Four CKD cats were randomized to receive placebo, with two cats crossing over to the MSC treatment group and one cat failing to co...
A recipe for mediocrity and disaster, in five axioms

Biomedical research in the US will become unsustainable unless scientists and research institutions start to question certain assumptions they have long taken for granted.
Effect of Flooding Depth on Growth, Biomass, Photosynthesis, and Chlorophyll Fluorescence of Typha domingensis

We examined the growth, biomass, photosynthesis, and chlorophyll fluorescence of Typha domingensis (southern cattail) in response to a six-week period of three flooding depths: 40, 91, and 137 cm above the soil surface and a subsequent four-week period of recovery at a 40-cm flooding depth. The 91- and 137-cm flooding significantly decreased the following: number of new shoots, number of live leaves, leaf, belowground and total biomass, and belowground biomass/leaf ratio. Plants flooded to a 91- or 137-cm depth had significantly lower chlorophyll concentration, photosynthesis, and fluorescence (Fv/Fm) as well as higher dark respiration and light compensation points than those exposed to the 40-cm flooding. Following the recovery period, most adverse impacts caused by the 91-cm flooding depth were reversed in terms of biomass, photosynthesis, and chlorophyll fluorescence, while the effect of the 137-cm flooding stresses exhibited by T. domingensis were not reversed. Flooding to a 137-cm depth is detrimental to T. domingensis and needs to be avoided. Our results indicate that depth-duration thresholds for management of T. domingensis dominated marshes are necessary to minimize deepwater impacts to vegetation communities.
Pinocytotic activity in ramified microglia

Pinocytotic activity was investigated in rat cerebral cortex using the soluble tracers horseradish peroxidase and Lucifer yellow. A subpopulation of cells selectively accumulated both compounds and the labelling was mainly present in pinocytotic vesicles associated with the cell body. Labelled cell bodies were small, round to oval, and distributed in an almost regular array throughout the tissue. Based on distinctive morphological features, some of the labelled cells could be determined as ramified microglia. This identification was confirmed by immunofluorescence staining with the monoclonal antibody OX-42, which specifically recognizes microglia; OX-42 staining consistently co-localized with pinocytotic labelling. The possibility that ramified microglial cells perform a normal function of continuous fluid exchange in brain tissue is discussed.
Observation of Spectral Broadening of Lower Hybrid Waves in Alcator C-Mod

Observations of the spectral broadening of lower hybrid (LH) waves in Alcator C-Mod are presented. We report the dependence of the pump broadening on two plasma parameters: plasma density and magnetic topology. As the plasma density was raised, we observed a significant increase of the pump broadening at 10 dB below the maximum peak. However, at the constant plasma density, when the magnetic topology was changed from the diverted plasma to the inner wall limited plasma, the spectral broadening was reduced. In an attempt to understand the causes of this variation, we report the change of density profiles in front of the LH launcher in two different magnetic topologies. The model analyses indicate that both the scattering process and parametric decay instability can contribute to the spectral broadening. Further experimental investigations are necessary to identify the causality between spectral broadening and the degradation of lower hybrid current drive efficiency at high density plasmas.
Opportunities for passive VHF radar studies of plasma irregularities in the equatorial E and F regions

Abstract Commercial FM broadcasts near 100 MHz provide powerful illumination of the ionosphere at a very useful wavelength. By performing synchronous observation of the transmitted signal and of scatter from the ionosphere, it is possible to produce excellent range and Doppler maps, and with additional antennas, interferometry may also be performed. Passive VHF radar has been successfully deployed at high latitudes to study auroral E region irregularities. At high latitudes the magnetic field geometry and strongly field-aligned nature of the irregularities restrict coherent scatter to the E region only, and only then near the poleward horizon. At the equator, however, these geometric issues permit observation of the E and F regions. Here we review the basic technique of passive radar, show some high latitude observations, and then lay out the scientific and experimental case for performing similar observations near the Earth's equator.
Democratic Legitimacy: The Limits of Instrumentalist Accounts

Political legitimacy is an important concept for democracies. Since the fundamental characteristic of any democracy is that through their collective decision-making, citizens are effectively the source of the political authority of the polity, it makes sense to ask when it can be said that a democratic polity is morally justified in exercising coercive political power over citizens. Understood in this way, legitimacy is linked to authority, the right to issue commands and enforce them through the use of coercive power. Questions about legitimacy apply at many different levels within any given democratic polity. If a question about legitimacy is asked of a particular government, the answer would, presumably, contain information about how the government or persons in question came to be or be in a position of power. Such a question can also be asked of the order or structure of a specific polity, of particular institutions within the structure, of specific laws or policies, and of an entire democratic polity. To raise a question of legitimacy with regard to an entire democratic polity is really nothing less than to ask why citizens should follow the laws of their society or affirm its order and actions as justifiable. Posing the question in this way reflects the nature of democracy as a political system which is rooted in the collective action of individuals aimed at establishing the terms according to which each person will be allowed to live freely. Democratic legitimacy therefore requires that the structure and actions of a democratic polity reflect this collective aim. Understood in this way, a question of legitimacy is open to a number of competing responses. This is reflected in the variety of conceptions of democratic legitimacy in contemporary democratic theory, which vary not just in how the question of legitimacy should be