cssi/SciSciGPT-SciSciNet huggingface dataset:
A fluorometric approach to the quantitation of cell number with application to a cell adhesion assay.

Abstract We describe a fluorometric approach to the determination of cell number. Cells are covalently labeled with fluorescein isothiocyanate (FITC) under physiologic conditions. Cells are lysed with detergent, and released fluorochrome is assessed quantitatively with a fluorescence spectrophotometer. Fluorescence varies linearly with regard to cell number over a wide range of concentrations, and allows detection of as few as 8 × 103 cells/ml. We describe the effect of different time and temperature incubations of FITC-labeled cells on fluorescence intensity, and we use the method to analyze the binding of peripheral blood mononuclear leukocytes to interferon-gamma-treated keratinocytes. Finally, we demonstrate that the results in an adhesion assay are comparable to those obtained with 51Cr-labeled cells. Quantitative fluorescence analysis of cell number offers a safe, inexpensive, rapid, and accurate method of determining cell number without the biological hazard and waste disposal problems associated with radioactive labeling.
Correspondence between a Linear Restriction and a Generalized Inverse in Linear Model Analysis

Abstract In experimental statistics the usual method of estimating treatment effects is to introduce arbitrary linear restrictions among the treatment effects in order to obtain solutions of the normal equations. A comparatively recent approach is to dispense with the linear restriction and use a generalized inverse solution to the normal equations. The present note is an attempt to bring these two methods closer together and show their correspondence; namely, for each given linear restriction, there exists a corresponding generalized inverse that yields the same solution for the treatment effects as the linear restriction does.
Analysis of the pharmacological properties of clozapine analogues using molecular electrostatic potential surfaces

Abstract Molecular electrostatic potential surfaces have been used to study a series of neuroleptic compounds, clozapine and clozapine analogues, with similar structures but two rather different pharmacological profiles. Using the electrostatic potential surfaces, the compounds studied could be assigned to one of two distinct categories corresponding to the two pharmacological classes. The results of this study suggest that the molecular electrostatic potential surfaces may be useful in the a priori prediction of pharmacological properties of untested clozapine analogues.
Hybrid grid generation for turbomachinery and aerospace applications

A hybrid prismatic/tetrahedral grid generation method is described and applied to complex turbomachinery and aerospace geometries. The high aspect ratio prismatic cells cover the region close to each body's surface for good resolution of viscous gradients, while tetrahedra tessellate the rest of the domain. The work introduces the concepts of multi-zone mesh generation and local variation of the number of prismatic layers (unstructured prism generation). Both these ideas are aimed to allow different levels of grid resolution within the same geometry and to treat disparate geometric length scales. The grid generator is tested with various complex geometries and the resulting hybrid meshes are presented. The applicability of the hybrid grid generator over the wide range of geometries with minimal user interaction demonstrates the robustness and universality of the method. The validity of the generated grids is tested via turbulent flow simulations. Copyright © 2000 John Wiley & Sons, Ltd.
The h-path distribution of the lifetime of conditioned Brownian motion for non-smooth domains

Consider the h-paths of Doob, and let τD be the lifetime of Brownian motion killed at ∂D, where D is a bounded Lipschitz (or NTA) domain in ℝn. then, $$\log P_x^h (\tau _D > t) \sim - \lambda _D t as t \to \infty $$ where λD is the first positive eigenvalue of-1/2Δ on D.
Cell Mechano-Sensing via Actomyosin Contractility

Cells are capable of sensing mechanical rigidity of surrounding environments. For example, cells have a tendency to produce higher levels of forces within more rigid extracellular matrices (ECMs). The mechano-sensing behaviors of cells are often accompanied by drastic reorganization of intracellular structures. It has been suggested that actin cytoskeleton, the scaffolding structure of eukaryotic cells mainly comprising F-actins, cross-linkers, and myosin motors, is involved with the mechano-sensing. The contractile force generated by the myosin motors is known to be sensitive to external mechanical environments, implying that the actomyosin contractility plays a significant role in the cell mechano-sensing. However, how microscopic properties of F-actins, cross-linkers, and myosins and their local interactions induce the macroscopic mechano-sensing behaviors of cells remains elusive. To elucidate the molecular mechanism, we developed an agent-based computational model of a three-dimensional cell-like structure where a thin actomyosin cortex beneath a membrane can be adhered to the ECM via focal adhesions. Our model accounts for several key features neglected by previous studies despite their potential significances for the mechano-sensing. Using the model, we evaluated time evolution of forces and ECM deformation generated by the cell-like structure. Both of the force and deformation increase over time, reaching a steady state. With softer ECM, the steady-state force is proportional to rigidity of the ECM but becomes insensitive to a change in the rigidity above a critical level of ECM rigidity, which is consistent with experiments. We elucidated the molecular mechanisms for the biphasic dependence on rigidity and overall mechano-sensing patterns based on the actomyosin contractility. We also systematically studied effects of the ECM rigidity on structural reorganization of actomyosin cortex.
Growth Hormone Receptor Is a Target for Presenilin-dependent γ-Secretase Cleavage

Growth hormone receptor (GHR) is a cytokine receptor superfamily member that binds growth hormone (GH) via its extracellular domain and signals via interaction of its cytoplasmic domain with JAK2 and other signaling molecules. GHR is a target for inducible metalloprotease-mediated cleavage in its perimembranous extracellular domain, a process that liberates the extracellular domain as the soluble GH-binding protein and leaves behind a cell-associated GHR remnant protein containing the transmembrane and cytoplasmic domains. GHR metalloproteolysis can be catalyzed by tumor necrosis factor-alpha-converting enzyme (ADAM-17) and is associated with down-modulation of GH signaling. We now study the fate of the GHR remnant protein. By anti-GHR cytoplasmic domain immunoblotting, we observed that the remnant induced in response to phorbol ester or platelet-derived growth factor has a reliable pattern of appearance and disappearance in both mouse preadipocytes endogenously expressing GHR and transfected fibroblasts expressing rabbit GHR. Lactacystin, a specific proteasome inhibitor, did not appreciably change the time course of remnant appearance or clearance but allowed detection of the GHR stub, a receptor fragment slightly smaller than the remnant but containing the C terminus of the remnant (receptor cytoplasmic domain). In contrast, MG132, another (less specific) proteasome inhibitor, strongly inhibited remnant clearance and prevented stub appearance. Inhibitors of gamma-secretase, an aspartyl protease, also prevented the appearance of the stub, even in the presence of lactacystin, and concomitantly inhibited remnant clearance in the same fashion as MG132. In addition, mouse embryonic fibroblasts derived from presenilin 1 and 2 (PS1/2) knockouts recapitulated the gamma-secretase inhibitor studies, as compared with their littermate controls (PS1/2 wild type). Confocal microscopy indicated that the GHR cytoplasmic domain became localized to the nucleus in a fashion dependent on PS1/2 activity. These data indicate that the GHR is subject to sequential proteolysis by metalloprotease and gamma-secretase activities and may suggest GH-independent roles for the GHR.
The effect of secondary effluents on eutrophication in Las Vegas bay, Lake Mead, Nevada

The eutrophication potential of Lake Mead, with primary emphasis on Las Vegas Bay, was determined with Selenastrum capricornutum. Nutrient limitation profiles were determined for three sampling stations in Las Vegas Bay and one in Boulder Basin. After heavy metals were chelated with EDTA, P was identified as the primary limiting nutrient with N the secondary limiting nutrient for S. capricornutum. Productivity potential was highest in upper Las Vegas Bay near the sewage inflow. Toward the mouth of the bay and in Boulder Basin, progressively lower potentials were defined. Productivity potential could not be predicted from the filtered samples because the nutrients bound up in the indigenous biomass remained on the filters. Autoclaving followed by filtration prior to assay enabled S. capricornutum to produce yields relative to the productivity observed in the lake.
The Role of a Conserved Lysine in Chloride- and Voltage-dependent ClC-0 Fast Gating

ClC-0 is a chloride channel whose gating is sensitive to voltage, chloride, and pH. In a previous publication, we showed that the K149C mutation causes a +70-mV shift in the voltage dependence of ClC-0 fast gating. In this paper we analyze the effects of a series of mutations at K149 on the voltage and chloride dependence of gating. By fitting our data to the previously proposed four-state model for ClC-0 fast gating, we show which steps in fast-gate opening are likely to be affected by these mutations. Computational analysis of mutant ClC-0 homology models show electrostatic contributions to chloride binding that may partially account for the effects of K149 on gating. The analysis of gating kinetics in combination with the available structural information suggests some of the structural changes likely to underpin fast-gate opening.
Folate targeting of haptens to cancer cell surfaces mediates immunotherapy of syngeneic murine tumors.

A variety of human cancers overexpress a cell surface receptor with high affinity for the vitamin, folic acid (Kd ~10–10 M). Covalent attachment of therapeutic agents to folic acid has been shown to allow efficient targeting of the folate–drug conjugates to folate receptor-expressing cancer cells, with little or no uptake by normal tissues except the kidneys. We report here the use of folate's ability to deliver attached molecules specifically to cancer cells to convert poorly immunogenic tumors into highly immunogenic tissue targets. By linking folic acid to a model hapten, we have been able to decorate folate receptor-expressing cancer cell surfaces with >106 haptens/cell in vivo. Following marking of such cells with haptens, the cells are observed to become opsonized with autologous anti-hapten antibodies, which is presumed to mediate cell removal via antibody-dependent cellular cytotoxicity (ADCC). Supplemental administration of low levels of ADCC-activating cytokines [e.g. interleukin-2 (IL-2) and interferon-alpha (IFN-α)] has been shown to synergize with the folate-targeted immunotherapy. Thus, using M109 syngeneic lung cancer cells injected intraperitoneally into Balb/c mice that were previously immunized against fluorescein, a significant extension of life span is observed following treatment with folate–fluorescein conjugates, and complete cures are observed upon supplementation with moderate levels of IL-2 and IFN-α. Because control tumor-bearing mice treated with the same cytokines but with non-targeted fluorescein show no extension of life span, we conclude that tumor-specific opsonization is an essential step in this immunotherapy. Finally, because the anti-fluorescein antibodies are unable to access the folate receptors on the apical membranes of the kidney proximal tubules, no kidney or other normal tissue cytotoxicity is observed. These data suggest that retargeting of haptens to folate receptor-expressing cancers might constitute a method for mobilizing the immune system specifically against poorly immunogenic tumors.
The human microbiome: ecosystem resilience and health

Given the importance of the microbiome for human health, both the stability and the response to disturbance of this microbial ecosystem are crucial issues. Yet, the current understanding of these factors is insufficient. Early data suggest there is relative stability in the microbiome of adults in the absence of gross perturbation, and that long-term stability of the human indigenous microbial communities is maintained not by inertia but by the action of restorative forces within a dynamic system. After brief exposures to some antibiotics, there is an immediate and substantial perturbation and at least a partial recovery of taxonomic composition. Responses to antibiotics are individualized and are influenced by prior experience with the same antibiotic. These findings suggest that the human microbiome has properties of resilience. Besides serving to reveal critical underlying functional attributes, microbial interactions, and keystone species within the indigenous microbiota, the response to disturbance may have value in predicting future instability and disease and in managing the human microbial ecosystem.
A Casein Kinase-Like Kinase Phosphorylates β-Tubulin and May Be a Microtubule-Associated Protein

The hypothesis that casein kinase II (CKII) is a microtubule-associated protein kinase was investigated using a neuronal cell line and bovine brain. Heparin, an inhibitor of CKII, inhibited the phosphorylation of a PC12 cytosolic protein whose molecular weight was similar to that of beta-tubulin. Partially purified PC12 CKII was immunoreactive to an antibody directed against bovine CKII and was able to phosphorylate purified beta-tubulin in a heparin-inhibitable manner when the concentration of tubulin was less than 50 micrograms/ml. To better determine if CKII is a microtubule-associated protein kinase, bovine brain tubulin was chromatographed on FPLC Mono Q and phosphocellulose columns. Several tubulin casein kinase (TCK) activities were apparent. All TCK activities phosphorylated tubulin and casein, but none was able to phosphorylate the CKII-specific synthetic peptide RRREEETEEE. One of these TCK fractions was immunoreactive to the antibody directed against CKII, and this antibody labeled a 50-kDa molecular mass band that had a molecular mass distinctly different from those of the subunits of CKII. Thus, we suggest that a CKII-like protein, but not CKII, might be a microtubule-associated protein.
Improved solution for laminar thermal boundary layers

first case was that of a heated plate with uniform temperature in the midst of an incompressible fluid with uniform velocity and temperature at infinity. The second case was that of an adiabatic plate also in a steady uniform flow of a fluid with uniform temperature. In a literature search, no previous work could be found, except for an analysis by L. Prandtl [2] in which no calculations of temperature distributions were included. Pohlhausen's analysis has become a classic of boundary layer methodology, but, for the calculations of temperature distributions, he used the data available at the time for the velocity distribution in the boundary layer [3]. This did not affect the expected qualitative trend of the temperature profiles which he determined for the two particular cases mentioned above. It is only when Pohlhausen's results are used to eonstruet the general solution for the thermal boundary layer that the inaceuracies in the veloeity profiles are large enough to distort some of the temperature profiles [4]. This occurs in a manner that can be easily deteeted as anomalous even by a relatively inexperienced observer. To facilitate the discussion, we summarize first the classieal treatment of the problem, and then show how possible wrong trends can be deteeted through a simplified qualitative analysis. This is aecomplished by establishing basie properties that the solution must possess. The governing equations for laminaI' flat-plate boundary layers without pressure gradient and buoyaney effeets, but with dissipation of energy, are: Introduction
Wake Acoustic Analysis and Image Decomposition via Beamforming of Microphone Signal Projections on Wavelet Subspaces

This paper describes the integration of wavelet analysis and time -domain beamforming of microphone array output signals for analyzing the acoustic emissions from airplane generated wake vortices. This integrated process provides visual and quantitative simultaneous information about the wake signal composition and array resolution for a particular wavelet subspace during a time interval , T. In the results section, an exam ple is given on how image processing algorithms might be used to automate the extraction of this information and select the wavelet subspaces from which to perform image reconstruction. This process begins with the projection of all the microphone signals on wavelet multi - resolution subspaces. The projections of these signals on the same wavelet subspace or scale are then beamformed to produce an image of the wake corresponding to that particular scale . Therefore for each time interval T, the process produc es a number of images equal to that of the wavelet s cales . This is equivalent to a more conventional Fourier -based idea of filtering the microphone signals with band -pass filters having non -uniform bandwidths then beamform in different sub -bands, but offer s greater flexibility and enhanced computational speed. Results from both approaches will be shown, which ultimately illustrate the advantage s of wavelet analysis over that of the Fourier -based analysis . Amongst the advantages are the speed of the decompos ition and ease of the image reconstruction from selected subspaces aided by the perfect reconstruction and orthogonality properties of wavelet analysis .
Safety and efficacy of the porcine small intestinal submucosa dural substitute: results of a prospective multicenter study and literature review.

Object Dural substitutes are often needed after neurosurgical procedures to expand or replace dura mater resected during surgery. A new dural repair material derived from porcine small intestinal submucosa (SIS) was evaluated in a prospective multicenter clinical study. Methods Between 2000 and 2003, 59 patients at five different institutions underwent dural reconstruction with the SIS dural substitute, with a minimum follow up of 6 months. The primary goals of the study were to assess the efficacy and safety of the SIS dural substitute according to the rate of cerebrospinal fluid (CSF) leakage, infection, and meningitis. Chiari malformation Type I decompression (32 patients) and tumor resection (18 patients) were the most common procedures performed, with 81% of SIS grafts implanted in the posterior fossa or spine. There was one case of a CSF leak (1.7%), two cases of wound infection (3.4%), and no cases of bacterial meningitis (0%) in the 58 patients available for follow up. In both cases of wound infec...
Cloning and characterization of the Vibrio cholerae genes encoding the utilization of iron from haemin and haemoglobin

Summary Vibrio cholerae can utilize haemin or haemoglobin as its sole source of iron. Four haem utilization mutants of a classical strain of V. cholerae were isolated. These mutations were complemented with pHUT1, a cosmid clone isolated from a library of wild-type CA401 DNA. Two independent Tn5 insertions into the cloned sequence disrupted function in all of the complemented mutants. Escherichia coli 1017 transformed with pHUT1 failed to utilize haemin as an iron source; a second plasmid containing a different cloned fragment of V. cholerae DNA (pHUT3) was required in addition to pHUT1 to reconstitute the system in E. coli. Minicell analysis and SDS-PAGE of protein fractions indicate that pHUT10 (a subclone of p>HUT1) encodes a 26 kDa inner membrane protein, and pHUT3 encodes a 77 kDa outer membrane protein. Loss of either protein by Tn5 mutagenesis abolishes haem utilization in E. coli. An E. coli hemA mutant that cannot synthesize porphyrins was transformed with the recombinant plasmids to determine whether the plasmids encoded the ability to transport the porphyrin as well as the iron. The transformants grew aerobically in media containing haemin, whereas the parental strain was unable to grow under these conditions. This indicates that V. cholerae haem-iron utilization genes allow transport of the entire haem moiety into the cell.
Tone and Voice: A Derivation of the Rules of Voice-Leading from Perceptual Principles

The traditional rules of voice-leading in Western music are explicated using experimentally established perceptual principles. Six core principles are shown to account for the majority of voice-leading rules given in historical and contemporary music theory tracts. These principles are treated in a manner akin to axioms in a formal system from which the traditional rules of voice-leading are derived. Nontraditional rules arising from the derivation are shown to predict formerly unnoticed aspects of voice-leading practice. In addition to the core perceptual principles, several auxiliary principles are described. These auxiliary principles are occasionally linked to voice-leading practice and may be regarded as compositional "options" that shape the music-making in perceptually unique ways. It is suggested that these auxiliary principles distinguish different types of part writing, such as polyphony, homophony, and close harmony. A theory is proposed to account for the aesthetic origin of voice-leading practices.
Incorporating thermal fluctuations into the immersed boundary method

We present a new computational method for simulating microscopic processes in physiology which accounts for stochastic thermal fluctuations and a dynamically evolving fluid environment. This latter feature is a principal advantage of our method relative to Brownian or Stokesian particle dynamics methods. Our approach builds on the “immersed boundary method” of Peskin, which simplifies the coupling between the fluid and the immersed particles and membranes so as to avoid complex boundary problems.
Allozyme markers in forest genetic conservation

Genetic diversity is important in tree-breeding, in managing rare and endangered tree species, and in maintaining healthy populations of widespread native tree species. Allozymes are useful in determining genetic relationships among species, where they can be used to assess affiliations of rare taxa and predict relative endangerment among species. Because allozymes sometimes yield different information about genetic variation within species than revealed by other traits, when estimates of total or adaptive genetic variation are important, allozymes are best used in conjunction with other traits. Allozymes are useful for measuring direct allelic diversity when designing ex-situ and in-situ conservation strategies. We demonstrate an application of canonical trend-surface analysis for determining locations of in-situ genetic conservation areas. Allozymes also serve as useful markers in monitoring the effects of forest management and other environmental changes on genetic diversity.
Anaerobic Respiration of Escherichia coli in the Mouse Intestine

The intestine is inhabited by a large microbial community consisting primarily of anaerobes and, to a lesser extent, facultative anaerobes, such as Escherichia coli, which we have shown requires aerobic respiration to compete successfully in the mouse intestine (S. A. Jones et al., Infect. Immun. 75:4891-4899, 2007). If facultative anaerobes efficiently lower oxygen availability in the intestine, then their sustained growth must also depend on anaerobic metabolism. In support of this idea, mutants lacking nitrate reductase or fumarate reductase have extreme colonization defects. Here, we further explore the role of anaerobic respiration in colonization using the streptomycin-treated mouse model. We found that respiratory electron flow is primarily via the naphthoquinones, which pass electrons to cytochrome bd oxidase and the anaerobic terminal reductases. We found that E. coli uses nitrate and fumarate in the intestine, but not nitrite, dimethyl sulfoxide, or trimethylamine N-oxide. Competitive colonizations revealed that cytochrome bd oxidase is more advantageous than nitrate reductase or fumarate reductase. Strains lacking nitrate reductase outcompeted fumarate reductase mutants once the nitrate concentration in cecal mucus reached submillimolar levels, indicating that fumarate is the more important anaerobic electron acceptor in the intestine because nitrate is limiting. Since nitrate is highest in the absence of E. coli, we conclude that E. coli is the only bacterium in the streptomycin-treated mouse large intestine that respires nitrate. Lastly, we demonstrated that a mutant lacking the NarXL regulator (activator of the NarG system), but not a mutant lacking the NarP-NarQ regulator, has a colonization defect, consistent with the advantage provided by NarG. The emerging picture is one in which gene regulation is tuned to balance expression of the terminal reductases that E. coli uses to maximize its competitiveness and achieve the highest possible population in the intestine.
Persistence of an Endemic (Toxigenic) Isolate of Clostridium difficile in the Environment of a General Medicine Ward

The epidemiology of Clostridium difficile-associated diarrhea (CDAD) in an endemic setting was investigated by use of DNA typing methods to determine the strain identity of C. difficile isolates. Two predominant toxigenic clones were found in the environment and accounted for 29.8% (type 1) and 15.5% (type 2) of CDAD cases, respectively. In endemic settings, the environment and cross-transmission may play a role in acquisition of CDAD.
The effects of wilt symptom development and peroxidase induction on interactions between vascular wilt bacteria and cucumber beetles

Infection of cucumber (Cucumis sativus L.) with the bacterial pathogen Erwinia tracheiphila E. F. Smith causes vascular wilt disease in leaves, which may alter the suitability of the host plant for insects and other pathogens. In this study, densities of spotted (Diabrotica undecimpunctata howardi Barber) and striped (Acalymma vittata (Fab.) cucumber beetles (Coleoptera: Chrysomelidae) were higher on wilted leaves of mature and seedling field plants inoculated with E. tracheiphila. Bacterial infection or feeding by D. undecimpunctata howardii beetles increased total peroxidase enzyme activity in inoculated or infested leaves of greenhouse seedlings, but only beetle feeding induced higher activities in untreated systemic leaves on the same plants. Neither bacterial infection nor beetle infestation led to the development of systemic acquired resistance (SAR) to the fungal pathogen Colletotrichum orbiculare (Berk & Mont.) Arx. Susceptibility to this fungus was greater on E. tracheiphila-infected plants than on controls. The positive association between leaf wilt symptom development and beetle occurrence thus occurs in the presence of an oxidative but not anti-pathogenic response induced by both the insect and the pathogen.
Refractory trigeminal neuralgia treatment outcomes following CyberKnife radiosurgery

A handful of studies have reported outcomes with CyberKnife radiosurgery (CKRS) for the treatment of trigeminal neuralgia. However, the follow-up has been short with no minimum follow-up required and have included patients with short duration of symptoms. Here we report our institutional experience on patients with a minimum follow-up of 1 year and a median follow-up of 28 months (mean 38.84 months). Twenty-five patients with medically and surgically intractable TN received CKRS with a mean marginal radiation dose of 64 Gy applied to an average isodose line of 86% of the affected trigeminal nerve. Follow-up data were obtained by clinical examination and telephone questionnaire. Outcome results were categorized based on the Barrow Neurological Institute (BNI) pain scale with BNI I-III considered to be good outcomes and BNI IV-V considered as treatment failure. BNI facial numbness score was used to assess treatment complications. A large proportion of patients (42.9%) reported pain relief within 1 month following CKRS treatment. The mean time to recurrence of severe pain was 27.8 months (range 1–129 months). At median follow-up of 28 months (mean 38.84 months), actuarial rate of freedom from severe pain (BNI ≥ III) was 72%. At last follow-up 2 (8%) patients had freedom from any pain and no medications (BNI I) and the majority (48%) had some pain that was adequately controlled with medications. Seven patients (28%) had no response to treatment and continued to suffer from severe pain (BNI IV or V). Patient’s diabetic status and overall post-treatment BNI facial numbness scores were statistically significant predictors of treatment outcomes. CKRS represents an acceptable salvage option for with medically and/or surgically refractory patients. Even patients with severely debilitating symptoms may experience significant and sustained pain relief after CKRS. Particularly, CKRS remains an attractive option in patients who are not good surgical candidates or possibly even failed surgical therapy. This data should help in setting realistic expectations for weighing the various available treatment options.
Developmental expression of cell cycle regulators in the baboon fetal adrenal gland.

Although the human and the nonhuman primate fetal adrenal glands undergo a highly unique pattern of cortical zonespecific intrauterine growth and development, studies of the regulatory components of the cell cycle responsible for this growth have not been conducted. Therefore, the present study determined expression of the cell cycle regulators, cyclin D1 and cyclin E, and their cyclin-dependent kinases, Cdk2, Cdk4, and Cdk6, and Ki67 a marker of cell proliferation within the baboon fetal adrenal cortex during advancing stages of gestation. Fetal adrenal glands were obtained on days 60 (early), 100 (mid), and 160‐170 (late) of gestation (termZ184 days). Mean (GS.E.) cyclin D1 mRNA levels, determined by RT-PCR and expressed relative to 18S rRNA, were similar at early (0 . 85G0 . 09) and mid (1 . 04G 0 . 08) gestation, then decreased (P!0 . 001, ANOVA) approximately 50% by late gestation (0 . 57G0 . 04). Cyclin E mRNA levels were also similar at early (2 . 03G0 . 07) and mid (1 . 63G0 . 31) gestation, and decreased by 70% (P!0 . 001) in late gestation (0 . 53G0 . 09). Coinciding with the decrease in cyclin D1 and cyclin E, the percentage of Ki67 positive cells in the definitive zone decreased twofold (P!0 . 01) between mid (28.2G3.6) and late (13.8G1.7) gestation. The cyclin D1 and cyclin E proteins, determined by immunocytochemistry, were expressed at high levels in the definitive zone of baboon fetal adrenal gland, where they decreased between mid- and late gestation. In contrast, immunocytochemical expression of the functionally important steroidogenic enzyme D 5 -3b-hydroxysteroid dehydrogenase (3b-HSD) became abundant in the definitive and transitional zones with advancing pregnancy. However, fetal adrenal Cdk2, Cdk4, and Cdk6 mRNA levels and protein immunoexpression were similar in the baboon fetal adrenal at early-, mid-, and late gestation. In summary, expression of cyclin D1, cyclin E, and Ki67 decreased, while 3b-HSD expression increased, in the fetal adrenal cortex, particularly in the definitive zone, between mid- and late-baboon gestation. We propose that a developmental decline in cellular proliferation permits functional differentiation offetal adrenal cortical cells, leading to increased production of steroid hormones important for placental estrogen synthesis and maturation of organ systems within the developing fetus.
On digraphs with the odd cycle property

We say that a digraph D has the odd cycle property if there exists an edge subset S such that every cycle of D has an odd number of edges from S. We give necessary and sufficient conditions for a digraph to have the odd cycle property. We also consider the analogous problem for graphs.
A Multilevel Modular Capacitor Clamped DC-DC Converter

A novel topology of multilevel modular capacitor clamped dc-dc converter (MMCCC) will be presented in this paper. In contrast to the conventional flying capacitor multilevel dc-dc converter (FCMDC), this new topology is completely modular and requires a simpler gate drive circuit. Moreover, the new topology has many advantageous features such as high frequency operation capability, low input/output current ripple, lower on-state voltage drop, and bi-directional power flow management. This paper discusses the construction and operation of the new converter along with a comparison with a conventional converter. Finally, the simulation and experimental results validate the concept of this new topology.
Effects of temperature, directional aspects, light conditions, and termite species on Subterranean termite activity (Isoptera: Rhinotermitidae)

Subterranean termite activity was investigated using field monitoring stations placed around 16 public schools in the triparish New Orleans metropolitan area of Louisiana. With the exception of one school, monitoring stations revealed the presence of Formosan subterranean termites. Native subterranean termites were found in six of the schools. The number of attacked monitoring stations varied significantly with light conditions at different directional aspects and termite species. For example, >50% of first-time attacked monitors by subterranean termites were at east with shade, north with shade, and south with shade placements. Formosan subterranean termites attacked a higher percentage of monitoring stations that were located in east with direct sun, east with shade, and north with direct sun. Native subterranean termites attacked a higher percentage of monitoring stations placed on south with direct sun, south with shade, and north with shade locations. Directional aspects at attacked monitoring stations by termites and corresponding average temperature at a depth of 10.2 cm from the foundation were not significantly correlated. Soil temperature readings 10.2 cm from the foundation did significantly affect seasonal foraging activity of subterranean termites.
Reconstructing Afghanistan: Civil–Military Experiences in Comparative Perspective

This edited volume sets out to accomplish a Herculean task: to describe and critically assess civil–military experiences in Afghanistan. Civil–military interaction is of course as old as warfare it...
Polymer Dynamics and Relaxation: Miscible polymer blends

Polymer blends account for about 40% of all polymers produced [1]. Miscible polymer blends are technologically important because they have the potential to lead to new materials without the expense and time of new synthesis. Like the metal alloys that preceded them, polymer blends often benefit from synergistic effects that make them more useful than a simple linear combination of properties would anticipate. The importance of miscible polymer blends is likely to increase as a result of environmental and economic pressures. Growth areas for miscible polymer blends include recycled polymers where understanding of and the ability to improve the properties of mixtures of post-consumer polymers could greatly increase the utility of these materials. Furthermore, use of miscible polymer blends for drug delivery and biomedical applications, where blending of materials already approved for in vivo applications in order to achieve improved properties without the time and expense associated with obtaining approval for use of new polymer materials, is receiving increased attention. An improved understanding of miscible blends may also ultimately have significant impact on our understanding of other dynamically heterogeneous polymer systems such as polymer nanocomposites, microphase separated polymer blends, and polymers in confined environments. The ability to understand, and ultimately to predict, the behavior of miscible polymer blends based upon the behavior of the pure component polymers that make up the blend is central to our ability to design polymer mixtures with desired properties.
Capture of Two Moth Species in Traps Placed at Different Heights in Sex Pheromone Treated Apple Orchards

Studies were conducted to compare the effect of trap placement above and below sex pheromone mating disruption (MD) dispensers on captures of codling moth, Cydia pomonella (L.), and oriental fruit moth, Grapholita molesta (Busck), in apple orchards. Traps were placed at a height of 1.8 m or 4.5 m in the tree canopy whereas MD dispensers were placed at 3.1 m within the tree canopy; an adjacent set of plots were treated similarly with only insecticides (nonMD). All trees were approximately 4.8 - 5.1 m in height. Capture of codling moth adults in traps was highest in traps placed at 4.5 m in both MD and nonMD plots and lowest in traps placed at 1.8 m in MD treated plots. Reduction in adult codling moth capture was low to moderate ( 70%) in traps placed below dispensers over both years. Oriental fruit moth adult capture in 2007 was lowest in traps placed at 1.8 m in plots treated with MD. In 2008, capture of oriental fruit moth was highest in traps placed at...
Molecular Pathology and Diagnostics of Childhood Tumors

Neoplasms in the fetus and infant are discussed in reference to types, incidence, clinical features, behavior, and response to treatment. Tumors that occur predominately in the first year of life have certain features of embryonic growth, including Wilms’ tumors, neuroblastomas, embryonic sarcomas, yolk sac tumors of the testis, hepatoblastomas, and medulloblastomas of the brain, as well as sacrococcygeal tumors that have an overgrowth of embryonic components. Chromosome translocations, tumor suppressor genes, and some syndromes and congenital malformations associated with childhood tumors are discussed.
Use of Comfortable Interpersonal Distance Scale in High School Students: Replication

To study the developmental aspects of psychological distance or personal space (2, 3, 4), the present authors developed a paper-and-pencil technique to assess the effects of differential stimuli on preferred interpersonal distance (1). Results indicated that persons of different races were always kept at greater distances than stimulus persons of the same race and that opposite-sex stimuli, in the adolescent population, were permitted to come closer than stimuli of the same sex. These sex differences, using the group-administered Comfortable Interpersonal Distance scale, were not unlike those previously reported (4). The present paper reports a replication using a different population of high school students. It was expected that findings would be repeated. Ss were 31 males and 31 females, aged 14 and 15 yr., from the student body of a suburban high school in the Southeast. The method was that described by Duke and Nowicki (1). Stimulus persons were black and white and male and female. Ss were required to indicate the distance at which they would feel comfortable with a stimulus person's closeness. Analysis of variance of distances indicated that, as in the first study, stimulus type significantly affected Ss' distance (P = 84.87, df = 3/180, p < ,001). When Neuman-Keuls' analyses were applied to these data, same sex-same race stimuli were held significantly farther away than stimulus persons of opposite sex but same race (M of 45.29 mm. and 15.87 mm. respectively); blacks of the opposite sex were held farther away than blacks of the same sex (M of 57.67 mm. and 46.43 mm. respectively, p = .05). These results replicate those observed in the original sample. Also, the interaction of sex of S by race was also significant (F = 5.21, df = 3/180, p = .01) . Males tended to keep aU stimuli farther away than females with the exception of persons of opposite sex-same race, i.e., white females. Again, this replicates an earlier result. The only finding which did not hold was direction of approach. In the initial sample, Ss preferred significantly greater distances when the stimulus persons approached from behind them and out of their field of vision. This effect did not occur for the present sample. Meisels and Guardo (4) have reported that this is a developmental phenomenon which begins to appear in adolescence. It may be that the variance of differences in developmental levels in the present sample washed out any consistent effects. Generally, the Comforrable Interpersonal Distance scale produced reasonable data from this sample. Study of different age groups may help determine whether the stability and validity of the measure makes it tenable for more extended use.
Effective bronchodilator resuscitation of children in the emergency room: device or interface?

Aerosol therapy is a vital component in the treatment of children with asthma, and inhaled β-agonists are the first-line therapy for bronchospasm in acute asthma. In the emergency department, bronchodilators are commonly administered to children via small-volume jet nebulizer (SVN) or large-volume
Consent and Assent in Pediatric Research: Whose Right Is It Anyway?

Although the right to health care is not written into the U.S. Constitution, moral and ethical tenets govern the delivery of optimal medical care universally and across the life continuum. Pertaining to children, in accordance with the Geneva Declaration of the Rights of the Child of 1924 and the United Nations Human Rights General Assembly adoption of the Rights of the Child in 1959, parents or guardians are responsible for the health and well-being of a child until age 18 years. Much consideration is needed regarding the anatomic, physiologic, emotional, and cognitive development of children when making decisions regarding their health care and, particularly, when enrolling them into research studies. .
[Problems during processing and storage of meat in cans. II. Chemical changes in canned meat with long storage time (author's transl)].

1. Bei der Sinnenprufung und nach dem Ergebnis der objektiven chemischen Untersuchung von langzulagernden Rindfleischkonserven in eigenem Saft erhielten die nach dem 4. Tage und nach dem 7. Tage nach dem Schlachten hergestellten Waren die beste Beurteilung, wobei die nach 7 Tagen hergestellte anfangs besser eingestuft wurde. Nach 2 Jahren Lagerzeit kehrte sich das Verhaltnis um. 2. Als Vergleichware wurden auch Rindfleischkonserven aus den Herstellungsjahren 1958–1962 nach einer Lagerzeit von 5 und 9 Jahren untersucht. Sie erwiesen sich im Geschmack als leer. strohig, teilweise auch bitter. Eine aus Gefrierfleisch (alte Herstellungsart mit lange gelagertem Gefrierfleisch ohne Schockgefrieren) hergestellte Ware erwies sich als besonders unangenehm im Geschmack, der als adstringierend und seifig beschrieben wurde. 3. Eine Gelfiltration der Diffusate aus den oben angefuhrten Rindfleischkonserven ergab eine Trennung von mit Ninhydrin anfarbbaren Stoffen in 2 deutlich getrennte Gipfel (Fraktion 90–130 und 170–230). Die 1. Fraktion wies das typische Aroma einer erhitzten Fleischware auf, wahrend die 2. einen ausgesprochen suslichen parfumahnlichen Geruch und Geschmack in konzentrierter Form besas. Nach Hydrolyse der 1. Fraktion wurde als Haupt-Zuckerkomponente Glucose, nach Spaltung der 2. Ribose neben anderen mit Anisidin-Phthalat anfarbbaren Stoffen gefunden. 4. Im Laufe der Lagerung nehmen die Stoffe des 1. Gipfels standig ab, wahrend die des 2. Gipfels nicht vollstandig verschwinden. Diese 2. Substanzgruppe scheint fur den anfanglichen Fleischgeschmack bei lang gelagerten Rindfleischkonserven verantwortlich zu sein. Eine ausgesprochene Haftung von Aromastoffen wie bei den Stoffen des 1. Gipfels ist jedoch nicht vorhanden. 5. Die Anfarbung der auf Peptidkarten aufgetrennten Peptide der unter 4. genannten Diffusate ergab mit Ninhydrin braun anfarbbare Stoffe, die konform mit dem Sinnenbefund wahrend der Lagerung der Konserven verschwinden.
Low-dose interleukin-2 impairs host anti-tumor immunity and inhibits therapeutic responses in a mouse model of melanoma

Recombinant interleukin-2 (rIL-2) is associated with objective responses in 15-20 % of patients with metastatic melanoma and renal cell carcinoma. More recently, rIL-2 has also demonstrated improved clinical activity in patients with melanoma. Given the toxicity of high-dose rIL-2 and the availability of many new immunotherapy agents, it has been suggested that lower doses of rIL-2 may be preferred for combination clinical studies. In order to determine the impact of low doses of rIL-2 on anti-tumor immunity and therapeutic effectiveness, we challenged C57BL/6 mice with poorly immunogenic B16-F10 melanoma and treated them with varying doses of rIL-2 (range 103-105 IU). Tumor growth at day 14 was significantly reduced when rIL-2 was administered at 10,000 (P < 0.02) and 100,000 (P < 0.02) IU doses, but tumor growth was significantly increased when mice were treated at 1000 IU rIL-2 (P < 0.02), as compared to placebo treatment. While the proportions of CD8+ and CD4+ T cells in the tumor were similar at all doses tested, the proportion of NK cells was decreased and the proportion of Tregs was increased in tumors exposed to low-dose rIL-2. The ratio of gp100-specific CD8+ to CD4+ regulatory T cells was increased in tumors treated at 10,000 and 100,000 IU of rIL-2 but was decreased at the 1000 IU dose compared to placebo-treated mice. These findings suggest that low-dose rIL-2 may impair host anti-tumor immunity and promote tumor growth. Early-phase adjuvant and combination clinical studies should include patient cohorts with higher doses of rIL-2.
Abstract LB-279: Quantitative flux measurements of serum protein catabolism in PDAC and other KRAS-mutant cancers

Activating KRAS mutations are prevalent in human cancer and are associated with poor prognosis. Among these malignancies is pancreatic ductal adenocarcinoma (PDAC), which is universally KRAS-driven and almost universally lethal. PDAC tumors are extremely fibrotic and hypovascularized, limiting perfusion of nutrients into the tumor, and tumor cells exhibit an altered metabolic program to support survival and proliferation in this environment. One metabolic activity upregulated in these tumor cells is the uptake and catabolism of serum protein. This process yields a substantial alternative source of amino acids and can support the proliferation of cultured cells lacking free essential amino acids. However, existing methods for assaying the uptake and degradation of intact protein provide qualitative outputs, and as such, do not yield accurate estimates of flux from serum protein to amino acid monomers. Here, we present a method for quantitative measurement of the catabolic production of amino acids from serum protein in cultured cells. By culturing cells in medium containing fully 13C-labeled glucose and amino acids supplemented with unlabeled albumin, we distinguish amino acids taken up as monomers from the medium from serum protein-derived amino acids. Using a variant of classical metabolic flux analysis, we derive flux estimates for serum protein catabolism from measurements of amino acid abundance and isotopic labeling over time. Our method is highly sensitive (i.e. can estimate “baseline” serum protein catabolism in KRAS wild-type cell lines) and yields precise estimates of amino acid influx from serum protein for all proteinogenic amino acids. We have measured serum protein catabolism in a variety of cultured cell lines and find that protein catabolism yields amino acids in comparable amounts to conventional uptake in various pancreatic and non-pancreatic lines. This approach enables estimation of protein catabolic flux in any cell line and can be used to assay the effects of various genetic and pharmacological perturbations on serum protein catabolism with high sensitivity and while accounting for growth rate differences. Citation Format: Michel Nofal, Kevin Zhang, Josh Rabinowitz. Quantitative flux measurements of serum protein catabolism in PDAC and other KRAS-mutant cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-279. doi:10.1158/1538-7445.AM2015-LB-279