cssi/SciSciGPT-SciSciNet huggingface dataset:
377. Intravascular Delivery of Adenovirus Vectors Rapidly Targets Platelets to the Reticuloendothelial System

Top of pageAbstract Following intravenous (iv) delivery of an adenovirus (Ad) vector a severely adverse event was seen in a phase I clinical trial. Systemic inflammatory response syndrome (SIRS) and biochemically detectable disseminated intravascular coagulation (DIC) were among complications that ultimately resulted in multiple organ system failure 98 hours after iv delivery of a dose of 6 x 1011 viral particles/kg. DIC is a complex clinical syndrome characterized by a systemic activation of coagulation leading to the intravascular deposition of fibrin in the (micro) vasculature and the simultaneous consumption of coagulation factors and platelets. Since platelet consumption is a symptom of DIC and Ad vectors are known to induce thrombocytopenia after iv delivery we decided to investigate Ad- platelet interactions as part of a safety and toxicity study. We investigated the interactions of an Ad5 vector, chimeric Ad5 vectors possessing the CD46 interacting Ad11 or Ad35 fibers (Ad5/F11 or Ad5/F35), and an Ad11 vector, early after iv delivery to mice. Transgenic mice that express human CD46 were injected in the tail vein with a total of 1011 viral particles of each vector. Within 10 minutes of iv delivery we found Ad particles associated with circulating platelets, with the highest levels seen with Ad11 vectors. Subsequently, different organs where monitored by immunohistochemistry and transmission electron microscopy (TEM) for evidence of in vivo Ad-platelet interactions. Within 5 minutes of administration degranulated platelets containing Ad5, Ad5/F11, Ad5/F35 or Ad11 vector particles could be seen directly interacting with endothelial cells within the liver sinusoids by TEM. Ad particles could also be seen within platelet aggregates and inside Kupffer cells. Triple label immunohistochemistry revealed widespread co-labeling of platelets (CD41), Kupffer cells (F4/80) and Ad (hexon) throughout the liver. In the spleen immunohistochemistry showed Ad particles in macrophage and platelet-rich areas of the marginal zone within 5 minutes. In the lung Ad genomes were found within 5 minutes with higher numbers of Ad11 genomes present. Widespread platelet accumulation was seen after delivery of all Ad vectors, with platelet-endothelial interaction and platelet aggregates visible throughout the pulmonary vasculature by immunohistochemistry and TEM. Polymorphonuclear cells and leukocytes within the pulmonary vasculature were also seen interacting with platelet aggregates. These data suggest that Ad and platelets interact rapidly after iv Ad delivery and that this interaction causes rapid targeting of platelets to the reticuloendothelial system. We are currently investigating the mechanisms of Ad-platelet interaction and subsequent platelet reticuloendothelial targeting.
Physiologic factors contributing to a transition in oral immunity among mechanically ventilated adults.

Ventilator-associated pneumonia (VAP), a specific type of nosocomial pneumonia, occurs in approximately 21% of patients in intensive care, and the mortality can be as high as 71%. VAP causes consid...
Rapid Method for Screening Large Numbers of Escherichia coli Colonies for Production of Plasmid-Mediated β-Lactamases

A rapid, simple assay for screening large numbers of Escherichia coli colonies for production of certain plasmid-mediated beta-lactamases (including TEM-1, TEM-2, HMS-1, SHV-1, OXA-1, PSE-1, PSE-4, and CEP-2) is described. The technique, a modification of the method of Slack et al. for detection of beta-lactamase in limited numbers of Haemophilus influenzae clinical isolates (Lancet ii:906, 1977), uses filter paper impregnated with benzylpenicillin and a pH indicator dye (bromocresol purple) that changes color in the presence of beta-lactamase activity. The test paper is briefly applied to an agar surface containing bacterial colonies which are subsequently scored individually on the paper by color: yellow indicates the presence of beta-lactamase, dark green its absence, and variegation (yellow and dark green) a mixed population. Concordance of the results of this assay with those of replica plating for antibiotic resistance was over 99%. Hundreds of colonies per plate can be scored quickly and remain viable for further evaluation. The assay appears to be useful for studies of the stability of plasmids encoding beta-lactamases and in cloning with vectors such as pBR322 in which insertion of DNA fragments can be detected by inactivation of the beta-lactamase gene. Whenever the assay is to be used, results should always be confirmed initially by another method, such as replica plating, because the test paper assay does not detect three beta-lactamases (OXA-2, OXA-3, and PSE-2) and also would miss intrinsic penicillin resistance.
Perspective on "exchange reactions with activation energy. I. Simple barrier potential for (H, H2)"

This paper provides an overview of the title paper by Karplus, Porter and Sharma, including a description of the history that led to this work, some details of the calculation and the results, and a discussion of subsequent developments in the field which were stimulated by this work.
Among the giants: Elihu Thomson: Man of many facets: This foremost inventor and industrialist also directed a corporate engineering and research department and was president of MIT

When he was still a high-school student. Elihu Thomson wrote, ?There is scarcely a day passing, on which some new use for electricity is not discovered. It seems destined to become at some future time the means of obtaining light, heat, and mechanical force.? In making this remark, Thomson could well have been anticipating his own future, for few men discovered more new uses for electricity than he. Along with Thomas A. Edison, George Westinghouse, and Charles Brush, Thomson helped create the first electric light and power systems. By the time of his death in 1937, he had come to be considered by the engineering profession as ?indisputably the dean of American electrical engineers.?
Iterative Methods for Best Approximate Solutions of Linear Integral Equations of the First and Second Kinds

Abstract Least-squares solutions of Fredholm and Volterra equations of the first and second kinds are studied using generalized inverses. The method of successive approximations, the steepest descent and the conjugate gradient methods are shown to converge to a least-squares solution or to the least-squares solution of minimal norm, both for integral equations of the first and second kinds. An iterative method for matrices due to Cimmino is generalized to integral equations of the first kind and its convergence to the least-squares solution of minimal norm is established.
The Effects of Reduction Potential and Number of Disulfide Bonds on the Correct Folding of Lin-12/Notch Repeats (LNRs) Using Human Notch 1 LNRA as a Model System

Notch receptors are multi-domain trans-membrane proteins that are important for cell-cell communication and development. Deregulated Notch signaling has been linked to many human diseases such as sclerosis, artereopathy and leukemia. The extra-cellular domain of the Notch Receptor contains the Ligand Binding Domain and the Negative Regulatory Region (NRR), which includes three Lin-12/Notch Repeats (LNR), small disulfide-rich sequences of 35 residues. It has been previously shown that the first LNR from human Notch1, hN1LNRA, requires Ca2+ and a certain reduction potential that ensures the correct formation of three specific disulfide bonds believed to be critical for LNR structure and function. However, the first LNR in human Notch 4 and some of the LNRs found in PAPP (pregnancy-associated plasma protein-A), only possess four cysteines thereby can only form two disulfide bonds.In this work we present our findings on the effect of various reduction potentials as well as the elimination of the first disulfide bond in the in vitro folding of hN1 LNRA through a comparative analysis. The kinetics of the folding process for both the wild-type and the four-cysteine mutant form of hN1LNRA is studied by trapping various folding intermediates in a time-course manner, which is possible due to the slow rate of disulfide bond formation. Our results indicate that even though the wild-type hN1LNRA is very tolerant to variations in the specific redox potential in obtaining its ultimate correct folding, the its folding kinetics is significantly impacted. This is in contrast to the mutant form, which does not fold into a single species under identical refolding conditions.
Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects in BMP7 deficient embryos

BMP7 is expressed at diverse sites in the developing mouse embryo, including visceral endoderm, notochord, heart, eye, kidney, and bone. A null mutation in BMP7 results in defects largely confined to the developing kidney and eye. To examine whether other bone morphogenetic protein (BMP) family members potentially substitute for BMP7 in mutant embryos, thereby restricting the observed defects, we analyzed the expression patterns of BMP2 through BMP7 in wild-type and mutant tissues. In the central nervous system and heart, which develop normally in the absence of BMP7 signaling, expression domains of other BMP family members completely overlap with that of BMP7. The variable expressivity of the eye defect correlates with partially overlapping BMP4 and BMP7 expression domains during early eye induction. The loss of BMP7 signaling in the kidney results in apoptosis in the metanephric mesenchyme, a cell population that exclusively expresses BMP7. Thus, tissue defects observed in BMP7 deficient embryos are restricted to cell populations exclusively expressing BMP7. These data suggest that BMP family members can functionally substitute for BMP7 at sites where they colocalize in vivo.
Retrograde Radioisotope Myocardial Perfusion Patterns in Dogs

A retrograde coronary vein injection technique for concentrating radioisotope in ischemic myocardial regions was evaluated in dogs. Potassium-43 in saline solution was injected into the coronary veins during complete closure of the coronary sinus. In the presence of coronary inflow obstruction, the venous potassium-43 was distributed mainly to the low pressure vessels in ischemic heart regions; i.e., the ratio of potassium-43 in the occluded-to-unoccluded areas ranged from 2:1 to 3:1 thirty seconds after retrograde injections. Krypton-85 in saline solution was injected under pressure into the coronary veins during partial closure of the coronary sinus. In the presence of inflow obstruction, the ratio of krypton-85 in the occluded- to-unoccluded areas ranged from 4:1 to 6:1 sixty seconds after retrograde injections; larger ratios may be expected after rapid washout of gas from the normally perfused region is nearly complete. Myocardial potassium-43 imaging techniques were applied to locate and measure the size of the ischemic heart region as a radioisotopic hot spot. Detection of hypoperfused areas of extremely small size may be accomplished by this technique.
Income Conservatism in the U.S. Technology Sector

We investigate the extent and nature of income conservatism as reflected in the financial statement numbers of firms in the U.S. technology sector. Technology firms are predicted to have greater income conservatism than other U.S. firms because they are subject to both higher shareholder litigation risk and conservative accounting standards such as SFAS 2. In the absence of a generally accepted measure of conservatism, we examine several proxies including loss incidence and accounting rates of return, operating cash flow and non-operating accrual levels, and regression coefficients from the income timeliness models in Basu (1997). Relative to other companies, technology firms are characterized by higher (and intertemporally increasing) levels of income conservatism. These differences are both statistically and economically significant. Further analysis suggests that technology firms' higher conservatism results primarily from conservative accounting rules for R&D expensing rather than shareholder litigation risk.
From divergent meanings to common practices: The early institutionalization of technology transfer in the life sciences at Stanford University

Abstract The formation of Stanford University's technology transfer program in the life sciences is analyzed from 1968 to 1982. The program evolved from multiple models based on divergent definitions of invention, inventor, rewards, and university–industry boundaries. The eventual program that emerged proved to be widely emulated. The norms of the academy shaped the uses of resources and the conditions of their appropriation. In turn, the currency of industrial science prompted the rethinking of academic norms. The analysis offers insight into the early stages of institutionalization, as the ambiguity of important categories and flexibility of policies were transformed into organizational routines. Today's ‘settled’ outcomes are the product of highly divergent practices.
Estradiol and tamoxifen reverse ovariectomy-induced physical inactivity in mice.

Decreased physical activity and increased body mass are associated with estrogen deficiency. Purpose: To determine whether estrogen or the estrogen analog, tamoxifen, could reverse those detrimental effects after surgical ovariectomy in mice. Methods: Ten-week-old C57BL/6 mice were sham operated (sham, N = 6) or ovariectomized (OVX, N = 9). After 4 wk of voluntary wheel running, placebo (OVX-P) or 17s-estradiol (OVX-E2) pellets were implanted and the mice ran an additional 4 wk. A second study followed in which mice received placebo, 17s-estradiol, or tamoxifen (OVX-Tam) simultaneously with ovariectomies. Distances run per 24 h and body masses were analyzed by two-way ANOVA with repeated measures. Results: During the initial 4 wk, OVX mice ran approximately 80% less and had approximately 20% greater body masses compared with sham mice (P < 0.001). Estradiol replacement quickly reversed the inactivity as OVX-E2 mice increased their running from 1.9 ± 0.3 km·24 h-1 to 6.9 ± 0.7 km within a week of replacement, which was equivalent to shams (8.1 ± 0.7 km), whereas OVX-P mice ran only 0.5 ± 0.2 km (P < 0.01). OVX-E2 mice tended to maintain body mass after estradiol replacement, whereas the OVX-P mice continued to increase mass. OVX mice that received tamoxifen had high running activity, approximately 9 km·24 h-1, and maintained body mass. Conclusion: The removal of ovarian hormones caused mice to become inactive and gain body mass. Hormone therapy in the form of 17s-estradiol or tamoxifen rapidly stimulated voluntary wheel running and reversed body mass gains, indicating that estrogen receptor binding was involved in regulating physical activity.
Production of interleukin-2 mRNA by bovine lymph node lymphocytes in response to concanavalin A, 12-O-tetradecanoylphorbol-13-acetate, and ionomycin.

Interleukin-2 (IL-2) is a lymphokine which, upon binding to its receptor, leads to the proliferation and differentiation of T-cells (helper, suppressor, and cytotoxic) and B-cells. While human and murine IL-2 have been extensively studied, less is known about bovine IL-2. In order to understand the induction of bovine IL-2 at the molecular level, we have examined IL-2 mRNA induction. The dose-responses and time courses of the production of IL-2 mRNA in response to Concanavalin A (ConA), 12-O-tetradecanoylphorbol-13-acetate (TPA), and ionomycin in lymph node lymphocytes (LNC) were determined. We found that high levels of IL-2 mRNA were produced in response to 1 μg ml−1 ConA plus 10−8 M TPA, but that even higher levels were produced in response to 1 μM ionomycin plus 10−8 M TPA. We also found that LNC stimulated with ConA displayed two phases of IL-2 mRNA production, one occurring approximately 2–4 h after stimulation and one occurring approximately 10 h after stimulation. However, in the presence of ConA plus TPA or ionomycin plus TPA the response was monophasic. IL-2 mRNA was detected within 2 h of addition of ConA plus TPA (the earliest time examined), reached maximum levels within 6 h, and declined to low levels after 12 h. IL-2 mRNA from LNC incubated with ionomycin plus TPA appeared within 2 h, and reached maximum levels at about 9 h. In contrast to the decrease seen after 12 h with ConA plus TPA, IL-2 mRNA from these cells remained high for 18 h and declined to low levels after 24 h.
Demonstration of an all-fiber acousto-optic tunable-filter-based spectrometer

We demonstrate a new all-fiber spectrometer based on acousto-optic tunable filter (AOTF) on cladding etched single-mode (SM) fiber. The spectrometer has a free spectral range (FSR) of 200 nm, a wavelength resolution of 2 nm, a dynamic range of 20 dB and a potential scanning rate of ~125 μs/sample. The spectrometer has the potential to be developed as a low-cost spectral monitoring device for dynamic gain equalizer (DGE) in Er-doped fiber amplifier modules.
Schwann Cell Proliferation and Macrophage Infiltration Are Evident at Day 14 after Painful Cervical Nerve Root Compression in the Rat

Abstract Although it is known that different types of nerve root insults can produce radicular pain, it is not known whether the neuronal and Schwann cell pathologies in the nerve root vary between inflammation-induced nerve root injury and traumatic compression. This study examined the extent of Wallerian degeneration and associated cellular repair processes in the nerve root in the context of mechanical hyperalgesia resulting from different modes of painful nerve root injury. The C7 dorsal nerve root underwent a transient 10 gram-force compression (10g), inflammation-induced irritation by chromic gut exposure (Cg), or a combination of those stimuli (10g+Cg). Fourteen days after injury when hyperalgesia remained, immunohistochemical analysis revealed upregulation of substance P, robust macrophage infiltration, myelin degeneration and debris removal, and a significant increase in the number of myelinating Schwann cells (Krox20-positive) in the compressed roots (10g, 10g+Cg). Cg alone also produced hyperal...
Variation at tri‐ and tetranucleotide repeat microsatellite loci in the fruit bat genus Cynopterus (Chiroptera: Pteropodidae)

There is considerable uncertainty surrounding the taxonomic relationship between Cynopterus sphinx and C. brachyotis, and the status of the many named forms within C. sphinx (Storz & Kunz 1999). Polymorphic microsatellite markers for cynopterine fruit bats would greatly aid efforts to elucidate species boundaries and genetic correlates of morphological variation within species. To assess levels of variation in C. sphinx and C. brachyotis, microsatellite genotypes were obtained for a total of 731 bats (620 C. sphinx and 111 C. brachyotis).
Valuing mortgage loan servicing

We develop an intertemporal model for valuing mortgage loan servicing contracts. The model includes a stochastic short-term interest rate and realized inflation rate which jointly determine the current mortgage coupon rate, the mortgagor's prepayment decision, the servicer's future net cash flows, and the rate at which to discount these future cash flows. Several potential uses of the model for institutions that service mortgages and trade servicing portfolios are illustrated by the application of the model to servicing fixed-rate mortgages and adjustable-rate mortgages. The model also is applicable to regulatory issues and to the servicing of other types of loans.
Factors affecting the regeneration of northern white cedar in lowland forests of the Upper Great Lakes region, USA

Abstract Regeneration of northern white cedar ( Thuja occidentalis ) has been poor in the Upper Great Lakes region for decades. To understand why, we used a spatially extensive approach to examine which factors limit regeneration in lowland swamp forests at a regional scale. We investigated patterns of seedling establishment and sapling recruitment in 1990–1991 and 1996 among 77 lowland stands distributed across northern Wisconsin and the eastern Upper Peninsula of Michigan. These stands differed in ownership, local site conditions, and ambient deer densities, allowing us to evaluate several factors potentially limiting regeneration. Lowland cedar seedlings in this region typically require 10 years to grow to 30 cm and 30 years to attain 3 m. Regression and path analyses demonstrate that initial seedling establishment increases in areas with greater seed input (as inferred from cedar basal area) and (in 1996) higher light levels. Subsequent recruitment to saplings +30 cm tall, however, depends far more on demographic inertia (the number of smaller seedlings) and escape from deer browsing. Surprisingly, estimated deer browse was as significant a factor as demographic inertia, reflecting cedar’s palatability, slow growth, and chronic high browsing pressure. Efforts to regenerate this species seem unlikely to succeed without significant and sustained reductions in deer density or extensive efforts to mechanically protect saplings from browsing.
Aspiration Pneumonitis following Electroconvulsive Therapy in Patients with Gastroparesis

Electroconvulsive therapy (ECT) has a role in the treatment of many depressed patients. It has consistently been found to be as effective (Crow 1984) and as safe (Pitts 1972) as pharmacological treatments for patients with major depression. For severe or psychotic depressions, ECT may well be the treatment of choice (Taylor 1982). Aspiration pneumonitis and adult respiratory distress syndrome (ARDS) have not been reported as complications of ECT, except when treatments were given without muscle relaxants (Perrin 1961). We recently observed two episodes of gastric aspiration associated with ARDS following ECT. Both patients were found to have loss of gastric muscle tone (gastroparesis). These findings suggest that candidates for ECT should be screened for gastroparesis, in addition to other well-recognized conditions that are associated with an increased risk of complications during or following ECT.
Beginning in English: The growth of linguistic and literate abilities in Spanish‐speaking first graders

Abstract This article traces the experience of two Spanish‐speaking children of Puerto Rican origin learning to read and write English as they learned to speak it in mainstream first‐grade classrooms in an urban school where instruction followed a basal series. One child read and wrote words with ease, though his ability to pronounce English and speak in grammatical sentences remained highly marked by Spanish. The other did not consolidate her reading and writing skills outside the structured activities, despite native‐like pronunciation and advancing English speech. Both showed through their engagement that they understood the spoken English of classroom but hardly the written English of texts. Their accomplishments in language and literacy are discussed in terms of issues in second language acquisition among school‐age children, differences between Spanish and English, metalinguistic features of instruction, and the content of early literacy learning.
Transport of folate compounds into Lactobacillus casei

Abstract Transport of folate, 5-methyl tetrahydrofolate, and amethopterin into Lactobacillus casei occurs against a concentration gradient, is pH and temperature dependent, requires glucose, exhibits saturation kinetics, is maximal when cells are harvested in late-log phase, and is repressed by excess folate in the growth medium. Km values are 0.35, 0.90, and 0.21 μ m for the influx of folate, 5-methyl tetrahydrofolate, and amethopterin, respectively. Dihydrofolate, tetrahydrofolate, 5-formyl tetrahydrofolate, 5-methyl tetrahydrofolate, aminopterin, and amethopterin are inhibitors of folate influx. Countertransport of 5-methyl tetrahydrofolate is enhanced by various other folate compounds. Uptake of folate, 5-methyl tetrahydrofolate, and amethopterin is inhibited to the same degree by increasing concentrations of iodoacetate. These results indicate that a single system is responsible for transport of a variety of folate compounds into L. casei.
Electrically Evoked Whole Nerve Action Potentials in Ineraid Cochlear Implant Users: Responses to Different Stimulating Electrode Configurations and Comparison to Psychophysical Responses

Electrically evoked whole nerve action potentials (EAP) have been recorded from 20 Ineraid cochlear implant users in response to bipolar and/or monopolar electrical stimulation of the cochlea. EAP ...
A Model-Based Approach for Making Ecological Inference from Distance Sampling Data

Summary We consider a fully model-based approach for the analysis of distance sampling data. Distance sampling has been widely used to estimate abundance (or density) of animals or plants in a spatially explicit study area. There is, however, no readily available method of making statistical inference on the relationships between abundance and environmental covariates. Spatial Poisson process likelihoods can be used to simultaneously estimate detection and intensity parameters by modeling distance sampling data as a thinned spatial point process. A model-based spatial approach to distance sampling data has three main benefits: it allows complex and opportunistic transect designs to be employed, it allows estimation of abundance in small subregions, and it provides a framework to assess the effects of habitat or experimental manipulation on density. We demonstrate the model-based methodology with a small simulation study and analysis of the Dubbo weed data set. In addition, a simple ad hoc method for handling overdispersion is also proposed. The simulation study showed that the model-based approach compared favorably to conventional distance sampling methods for abundance estimation. In addition, the overdispersion correction performed adequately when the number of transects was high. Analysis of the Dubbo data set indicated a transect effect on abundance via Akaike's information criterion model selection. Further goodness-of-fit analysis, however, indicated some potential confounding of intensity with the detection function.
Photodynamic modulation of wound healing with BPD-MA and CASP.

Background and Objective Wound healing is an intricate process requiring the orchestration of cells, growth factors, cytokines, and the extracellular matrix. Cytokines, specifically TGF-β, are believed to be instrumental in sustaining the fibrotic process, which leads to scarring. Photodynamic therapy (PDT) uses potent photosensitizers, which induce a wide range of effects on cells and the extracellular matrix. The influences of PDT on wound healing are not well known. Study Design/Materials and Methods Seven full-thickness incisional wounds were placed on each of 24 hairless Sprague Dawly rats, three wounds on one flank serving as dark controls and four on the contralateral side treated with PDT. Wounds were created two days before, one hour before, or one hour after red light exposure with an argon ion pumped dye laser. Twelve rats were injected with 0.25 mg/kg or 0.5 mg/kg of the PDT drug, BPD-MA, and the other 12 with 5 mg/kg or 10 mg/kg of the PDT drug, CASP, 3 and 24 hours prior to irradiation of light, respectively. At low doses of both photosensitizers, animals were irradiated with 1, 5, 10, and 20 J/cm2. At higher doses of BPD-MA and CASP animals were treated with 10, 20, 50, and 100 J/cm2 of light. Wounds were examined each day for 14 days and noted for edema, erythema, inflammation, necrosis, and quality of scarring. Wounds were also photographed at day 0, 2, 5, 8, and 14 post-irradiation. All animals were sacrificed 14 days after irradiation and the wounds were evaluated by light microscopy. Results Grossly, animals treated with 0.25 mg/kg BPD-MA showed no effect with PDT. Animals treated with 0.5 mg/kg BPD, and 5 and 10 mg/kg CASP showed responses that varied with both light and drug dose. Erythema, edema, inflammation, and necrosis attributed to PDT were all observed, but there was no apparent influence of PDT on either the rate or final appearance of wound healing. Histologically, there were no apparent differences between treated and untreated sites, regardless of the drug, dose of light, or time of irradiation. Conclusion A single PDT treatment given before or after skin wounds does not apparently alter wound healing even when PDT caused brisk inflammatory reactions. PDT may have effects that were not detected. We conclude that PDT does not greatly influence incisional skin wound healing in the rat model. Lasers Surg. Med. 24:375–381, 1999. © 1999 Wiley-Liss, Inc.
Non-linear analysis of adhesively bonded joints

Abstract An updated Lagrangian formulation is used to develop a 2-D finite element for the analysis of adhesively bonded joints. The finite element accounts for the geometric non-linearity. The present finite element results are in good agreement with those reported in the literature. The effect of boundary conditions and mesh on the stress distributions in lap joints is also investigated.
ELECTRON MICROSCOPIC LOCALIZATION OF ACID PHOSPHATASE AND THIAMINE PYROPHOSPHATASE ACTIVITY IN HYPOTHALAMIC NEUROSECRETORY CELLS OF THE RAT.

Supraoptic nuclei in the hypothalamus of rats were fixed for the electron microscope by vascular perfusion with solutions of glutaraldehyde followed by post fixation with osmium tetroxide. Cytochemical methods for detection of acid phosphatase and thiamine pyrophosphatase activity have been applied to glutaraldehyde-fixed frozen sections containing the neurosecretory cells. The enzyme activities have been localized to certain Golgi cisternae. Acid phosphatase activity is present in the large (0.4 µ to 1.0 µ) granules or dense bodies which are surrounded by a single limiting membrane; both features characterize these structures as lysosomes. Smaller (0.1 µ) granules also present in the perikarya are generally unreactive towards enzyme activity and resemble in form the neurosecretory granules in the neurohypophysis.
WE-C-224C-01: Buried Emanation: The Dawn of Prostate Brachytherapy

Although radical prostatectomy was introduced in 1905, few cases of prostate cancer were diagnosed at a stage amenable to curative resection. Megavoltage equipment that could safely deliver a curative dose of radiation to the prostate did not become widely available until the 1960's. To fill this therapeutic void, leading urologists often turned to brachytherapy. This presentation follows the development of intracavitary and interstitial techniques during the second and third decades of the 20th century.
Ceste figure contient tout le royaulme de France. Cartography and national identity in France at the end of the Hundred Years War

This paper examines a little known map of France made around the middle of the fifteenth century, for a genealogical manuscript of the text known as A tous nobles, conserved today as Bibliotheque nationale de France [BnF] MS fr. 4991. It argues that the map's prominence in the manuscript articulates a notion of French identity based on a bond to the territory of France rather than on fealty to its king. Using other images from the manuscript, it considers the importance of geography to the emergence of French national sentiment at the time of the Hundred Years War.
Characteristics of the water cycle and land-atmosphere interactions from a comprehensive reforecast and reanalysis data set: CFSv2

The behavior of the water cycle in the Coupled Forecast System version 2 reforecasts and reanalysis is examined. Attention is focused on the evolution of forecast biases as the lead-time changes, and how the lead-time dependent model climatology differs from the reanalysis. Precipitation biases are evident in both reanalysis and reforecasts, while biases in soil moisture grow throughout the duration of the forecasts. Locally, the soil moisture biases may shrink or reverse sign. These biases are reflected in evaporation and runoff. The Noah land surface scheme shows the necessary relationships between evaporation and soil moisture for land-driven climate predictability. There is evidence that the atmospheric model cannot maintain the link between precipitation and antecedent soil moisture as strongly as in the real atmosphere, potentially hampering prediction skill, although there is better precipitation forecast skill over most locations when initial soil moisture anomalies are large. Bias change with lead-time, measured as the variance across ten monthly forecast leads, is often comparable to or larger than the interannual variance. Skill scores when forecast anomalies are calculated relative to reanalysis are seriously reduced over most locations when compared to validation against anomalies based on the forecast model climate at the corresponding lead-time. When all anomalies are calculated relative to the 0-month forecast, some skill is recovered over some regions, but the complex manner in which biases evolve indicates that a complete suite of reforecasts would be necessary whenever a new version of a climate model is implemented. The utility of reforecast programs is evident for operational forecast systems.
Peroxide−Acetic Acid Pretreatment To Remove Bagasse Lignin Prior to Enzymatic Hydrolysis

This paper presents results on the features of bagasse pretreatment with peroxide and acetic acid (peroxide−HAc) aiming at selective removal of lignin to enhance enzymatic hydrolysis. Surface response methodology was employed to study the effects of major process parameters on delignification and to establish a model for the prediction of lignin removal in the process. Enzymatic hydrolysis following the pretreatment was conducted to evaluate the enhancement of biohydrolysis by the pretreatment. Results revealed that peroxide−HAc pretreatment of bagasse retained most of the carbohydrate constituents, although the delignification rate was low. Peroxide−HAc concentration, temperature, and time demonstrated significant effects on bagasse lignin removal. The relationship between lignin removal and the process parameters could be well described by a mathematical model derived from the experimental data. After treatment with 69.1% peroxide−HAc at 80 °C for 26.5 h, 97.08% of lignin could be removed while keeping ...
The rostromedial tegmental nucleus modulates behavioral inhibition following cocaine self-administration in rats.

Recent findings suggest that the mesolimbic dopamine neurons, known to promote cocaine-seeking behavior, are strongly inhibited by a newly characterized region of the midbrain known as the rostromedial tegmental nucleus (RMTg). The RMTg appears to be involved in generating reward-prediction error signals and inhibition of motivated behaviors, suggesting its potential involvement in the extinction of cocaine seeking as well. Therefore, to address this question, male Sprague–Dawley rats underwent surgeries for implantation of catheters and cannulas targeted at the RMTg. After cocaine self-administration, rats underwent modified extinction training. Pre- or post-training intra-RMTg microinjections of the allosteric AMPA receptor potentiator PEPA during the first 5 days of extinction training appeared to enhance the retention of the extinction learning. Following the extinction training, rats underwent cue-induced reinstatement or an ‘inactivation-alone' extinction tests. RMTg inactivation before a cue-induced reinstatement session or inactivation alone before a standard extinction session increased overall lever pressing. To determine whether these effects generalized to other motivated behaviors, additional experiments examining food-seeking behavior were also conducted. The results from the food-seeking experiments indicate that PEPA microinjections into the RMTg did not influence the extinction of food seeking and that, at least in rats that had not been given PEPA during the extinction learning experiments, RMTg inactivation had no effect on lever pressing during the cue-induced reinstatement or inactivation-alone tests. These findings suggest that the RMTg provides general behavioral inhibition and is potentially involved in learning to extinguish cocaine-seeking behavior in rats.
Shell-Model Calculations for A = 6 − 14 Nuclei with a Realistic Interaction

Shell-model calculations are performed on the normal parity states of $0p$-shell nuclei with $A=6\ensuremath{-}14$. The Hamiltonian is diagonalized in the full $0p$ basis, and the effective two-body interaction is computed from the Sussex relative harmonic-oscillator matrix elements. The second-order corrections to the two-body matrix elements are calculated for all intermediate states up to $2\ensuremath{\hbar}\ensuremath{\omega}$ excitation energy. The harmonic-oscillator size parameter is taken to be constant at 1.7 fm for all nuclei, and the ${p}_{\frac{3}{2}}\ensuremath{-}{p}_{\frac{1}{2}}$ single-particle energy splitting is determined for each mass number by a least-squares rms fitting to the experimental spectrum. Static and dynamic properties of the energy levels are calculated and found to be usually in good agreement with experiment.
Radio occultation by Saturn's rings - Observations of structure and particle size with Voyager 1

Voyager 1 radio occultation study of Saturn's rings gives detailed information regarding the rings' radial structure and particle sizes. Structure within the rings is mapped to a radial resolution of few hundred m in the tenuous parts of ring C and the Cassini Division, and few km over most of ring A. Fine resolution profiles reveal extremely sharp edges, very narrow gaps, and a host of wave phenomena. Particle size distributions obtained from occultation data within several ring regions are roughly consistent with an inverse cube power law with upper size cutoff in the 5 to 10 m radius range.
Deletion of tenascin-C gene exacerbates atherosclerosis and induces intraplaque hemorrhage in Apo-E-deficient mice.

Abstract Aims Tenascin-C (TNC), a matricellular protein, is up-regulated in atherosclerotic plaques. We investigated whether the deletion of TNC gene affects the development of atherosclerosis in a murine model. Methods TNC−/−/apo E−/− mice were generated and used for atherosclerosis studies. We compared these results to those observed in control groups of apo E−/− mice. Results The en face analysis of aortic area showed that the mean aortic lesion area of the double knockout (KO) mice was significantly higher than that of control mice at different times after feeding of atherogenic diet; the accumulation of lesional macrophages and lipids was significantly higher. Analysis of cell adhesion molecules revealed that vascular cell adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1, was up-regulated 1 week after feeding of atherogenic diet in the double KO mouse as compared to apo E−/− mouse. Cell culture studies revealed that the expression of VCAM-1 in endothelial cells isolated from the double KO mouse is more sensitive to the tumor necrosis factor α stimulation than the cells isolated from apo E−/− mice. Cell adhesion studies showed that the adherence of RAW monocytic cells to the endothelial cells was significantly enhanced in the cultured endothelial cells from the TNC gene-deleted cells. Following the prolonged feeding of an atherogenic diet (28–30 weeks), the aortic and carotid atherosclerotic lesions frequently demonstrated large grossly visible areas of intraplaque hemorrhage in the double KO mice compared to control. Conclusions These data unveil a protective role for TNC in atherosclerosis and suggest that TNC signaling may have the potential to reduce atherosclerosis, in part by modulating VCAM-1 expression.
Effects of the permeability enhancers, tetradecylmaltoside and dimethyl-β-cyclodextrin, on insulin movement across human bronchial epithelial cells (16HBE14o−)

Abstract The permeability of human bronchial epithelial cells (16HBE14o−) to radiolabelled insulin ([125I]insulin) formulated in the absence or presence of two different saccharide-containing permeability enhancers was investigated. In the absence of either enhancer, mannitol permeability and transepithelial electrical resistance (RTE) remained essentially unaffected for the duration of a 2-h experiment. Addition of either 0.125% tetradecylmaltoside (TDM) or 1% dimethyl-β-cyclodextrin (DMBCD) to the apical surface of cells resulted in increased mannitol permeability and decreased RTE, suggesting a loosening of cellular tight junctions and a concomitant increase in paracellular movement. Addition of [125I]insulin to the apical side of 16HBE14o− cells in the absence or presence of 1% DMBCD resulted in little or no [125I]insulin movement to the basolateral chamber or degradation in the apical chamber. However, in the presence of 0.125% TDM, the amount of intact [125I]insulin remaining in the apical chamber was substantially decreased, while [125I]insulin and 125I-labeled fragments were recovered on the basolateral side of the cells after 2 h. These findings provide evidence that the loosening of the tight junctions between cells achieved with DMBCD is not sufficient to stimulate transepithelial insulin movement, whereas exposure to 0.125% TDM causes an increase in [125I]insulin permeation and degradation.
Intranuclear Microinjection of DNA into Dissociated Adult Mammalian Neurons

Primary neuronal cell cultures are valuable tools to study protein function since they represent a more biologically relevant system compared to immortalized cell lines. However, the post-mitotic nature of primary neurons prevents effective heterologous protein expression using common procedures such as electroporation or chemically-mediated transfection. Thus, other techniques must be employed in order to effectively express proteins in these non-dividing cells. In this article, we describe the steps required to perform intranuclear injections of cDNA constructs into dissociated adult sympathetic neurons. This technique, which has been applied to different types of neurons, can successfully induce heterologous protein expression. The equipment essential for the microinjection procedure includes an inverted microscope to visualize cells, a glass injection pipet filled with cDNA solution that is connected to a N2(g) pressure delivery system, and a micromanipulator. The micromanipulator coordinates the injection motion of microinjection pipet with a brief pulse of pressurized N2 to eject cDNA solution from the pipet tip. This technique does not have the toxicity associated with many other transfection methods and enables multiple DNA constructs to be expressed at a consistent ratio. The low number of injected cells makes the microinjection procedure well suited for single cell studies such as electrophysiological recordings and optical imaging, but may not be ideal for biochemical assays that require a larger number of cells and higher transfection efficiencies. Although intranuclear microinjections require an investment of equipment and time, the ability to achieve high levels of heterologous protein expression in a physiologically relevant environment makes this technique a very useful tool to investigate protein function.
Developmental competence of bovine embryos from heat-stressed ova.

Because multiple ovulation embryo transfer procedures are occasionally performed in cows experiencing heat stress, the goal of this study was to assess the developmental competence of otherwise morphologically normal embryos from heat-stressed ova. To this end, the ability of compact morulae from heat-stressed and non-heat-stressed bovine ova to undergo blastocyst development after culture at 38.5 or 41.0°C was examined. It was hypothesized that heat-induced perturbations in the ooplasm carry over to increase the susceptibility of the preattachment embryo to heat stress. Initially, ova were matured at 38.5 or 41.0°C. The consequences of heat stress did not include altered cleavage, but did reduce the proportion of 8- to 16-cell-stage embryos (55.3 vs. 50.6%; SEM ± 1.9). Although proportionately fewer, compact morulae from heat-stressed ova were equivalent in quality to those from non-heat-stressed ova (2.1 and 2.1; SEM = 0.04). Culture of compact morulae from non-heat-stressed ova at 41.0°C did not affect blastocyst development (71.9 and 71.5%; SEM = 3.0). Furthermore, the development of compact morulae from heat-stressed ova was similar to that of non-heat-stressed ova after culture at 38.5°C (68.2 vs. 71.9 and 71.5%; SEM = 3.0). However, blastocyst development was reduced when compact morulae from heat-stressed ova were cultured at 41.0°C (62.3 vs. 71.9, 71.5 and 68.2; SEM = 3.1). In summary, reduced compaction rates of heat-stressed ova explained in part why fewer develop to the blastocyst stage after fertilization. The thermolability of the few embryos that develop from otherwise developmentally challenged ova emphasizes the importance of minimizing exposure to stressor(s) during oocyte maturation.
Architecture Concepts for a Future Heterogeneous, Survivable Tactical Internet

A new internetworking architecture is needed to support tactical operations and survive close contact with a peer adversary while interconnecting heterogeneous subnetworks (RF, SATCOM, optical, etc.) where the limiting resource varies over time. This paper describes the results of a DARPA study that investigated what an Internet with these properties would look like if not constrained by the current Internet design. Five architectural components were identified which can work together to provide the necessary capabilities. Each is described and the research gaps required to develop it are identified. A set of new network-level behaviors, essential for future tactical operations, are described and mapped to the architecture. The paper is intended to initiate dialog with the networking community to help define potential future research in this area.
Successful treatment of malignant rhabdoid tumor of the vulva in an older patient: a case report and review of the literature.

Abstract PURPOSE: Malignant rhabdoid tumor (MRT) of the vulva is a rare and very aggressive neoplasm. Only 7 cases have been reported thus far in the English literature. This case reports the oldest patient to date with MRT. This 63 year old was successfully treated with surgery and radiation therapy. The current literature is reviewed, and different treatment modalities are considered and evaluated.
Life and Death of Sensory Hair Cells Expressing Constitutively Active TRPML3

The varitint-waddler mutation A419P renders TRPML3 constitutively active, resulting in cationic overload, particularly in sustained influx of Ca2+. TRPML3 is expressed by inner ear sensory hair cells, and we were intrigued by the fact that hair cells are able to cope with expressing the TRPML3(A419P) isoform for weeks before they ultimately die. We hypothesized that the survival of varitint-waddler hair cells is linked to their ability to deal with Ca2+ loads due to the abundance of plasma membrane calcium ATPases (PMCAs). Here, we show that PMCA2 significantly reduced [Ca2+]i increase and apoptosis in HEK293 cells expressing TRPML3(A419P). The deaf-waddler isoform of PMCA2, operating at 30% efficacy, showed a significantly decreased ability to rescue the Ca2+ loading of cells expressing TRPML3(A419P). When we combined mice heterozygous for the varitint-waddler mutant allele with mice heterozygous for the deaf-waddler mutant allele, we found severe hair bundle defects as well as increased hair cell loss compared with mice heterozygous for each mutant allele alone. Furthermore, 3-week-old double mutant mice lacked auditory brainstem responses, which were present in their respective littermates containing single mutant alleles. Likewise, heterozygous double mutant mice exhibited severe circling behavior, which was not observed in mice heterozygous for TRPML3(A419P) or PMCA2(G283S) alone. Our results provide a molecular rationale for the delayed hair cell loss in varitint-waddler mice. They also show that hair cells are able to survive for weeks with sustained Ca2+ loading, which implies that Ca2+ loading is an unlikely primary cause of hair cell death in ototoxic stress situations.