cssi/SciSciGPT-SciSciNet huggingface dataset:
Multifunctional FeCo-graphitic carbon nanocrystals for combined imaging, drug delivery and tumor-specific photothermal therapy in mice

Ultrasmall FeCo-graphitic carbon shell nanocrystals (FeCo/GC) are promising multifunctional materials capable of highly efficient drug delivery in vitro and magnetic resonance imaging in vivo. In this work, we demonstrate the use of FeCo/GC for highly effective cancer therapy through combined drug delivery, tumor-selective near-infrared photothermal therapy, and cancer imaging of a 4T1 syngeneic breast cancer model. The graphitic carbon shell of the ∼4 nm FeCo/GC readily loads doxorubicin (DOX) via π-π stacking and absorbs near-infrared light giving photothermal heating. When used for cancer treatment, intravenously administrated FeCo/GC-DOX led to complete tumor regression in 45% of mice when combined with 20 min of near-infrared laser irradiation selectively heating the tumor to 43–45 °C. In addition, the use of FeCo/GC-DOX results in reduced systemic toxicity compared with free DOX and appears to be safe in mice monitored for over 1 yr. FeCo/GC-DOX is shown to be a highly integrated nanoparticle system for synergistic cancer therapy leading to tumor regression of a highly aggressive tumor model. Open image in new window
Alleviation of systemic manifestations of multicentric Castleman's disease by thalidomide.

Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder of unknown etiology. Although HHV-8 (human herpesvirus type 8) has been suggested as a possible etiologic agent in a subpopulation of cases, appropriate treatment of the HHV-8 infection has not produced regression of the disease. Additionally, other treatment modalities, including steroids and various regimens of chemotherapy, do not consistently provide good control of the disease. Clinical signs and symptoms of the disease are primarily mediated by cytokines, especially interleukin-6 (IL-6). We report a case of multicentric Castleman's disease that responded dramatically to single agent thalidomide. A powerful cytokine disruptor, thalidomide may have good therapeutic efficacy in treating MCD and related cytokine-mediated disorders. Am. J. Hematol. 73:48–53, 2003. © 2003 Wiley-Liss, Inc.
Decreased antibody response to influenza vaccination in kidney transplant recipients: a prospective cohort study.

Background Antibody response to the inactivated influenza vaccine is not well described in kidney transplant recipients administered newer, but commonly used, immunosuppression medications. We hypothesized that kidney transplant recipient participants administered tacrolimus-based regimens would have decreased antibody response compared with healthy controls. Study Design Prospective cohort study of 53 kidney transplant recipients and 106 healthy control participants during the 2006-2007 influenza season. All participants received standard inactivated influenza vaccine. Setting & Participants Kidney transplant recipients administered tacrolimus-based regimens at a single academic medical center and healthy controls. Predictor Presence of kidney transplant. Outcomes Proportion of participants achieving seroresponse (4-fold increase in antibody titer) and seroprotection (antibody titer ≥ 1:32) 1 month after vaccination. Measurements Antibody titers before and 1 month after vaccination by means of hemagglutinin inhibition assays for influenza types A/H1N1, A/H3N2, and B. Results A smaller proportion of the transplantation group compared with the healthy control group developed the primary outcomes of seroresponse or seroprotection for all 3 influenza types at 1 month after vaccination. The response to influenza type A/H3N2 was statistically different; the transplantation group had 69% decreased odds of developing seroresponse (95% confidence interval, 0.16 to 0.62; P = 0.001) and 78% decreased odds of developing seroprotection (95% confidence interval, 0.09 to 0.53; P = 0.001) compared with healthy controls. When participants less than 6 months from the time of transplantation were considered, this group had a significantly decreased response to the vaccine compared with healthy controls. Limitations Decreased sample size, potential for confounders, outcome measure used is the standard but does not give information about vaccine efficacy. Conclusions Kidney transplant recipients, especially within 6 months of transplantation, had diminished antibody response to the 2006-2007 inactivated influenza vaccine.
Formaldehyde Oxidation over Ag Catalysts

H2CO oxidation was studied over Ag powder, high surface area (HSA) α-alumina, and Ag dispersed on both (HSA) α-Al2O3 and SiO2. Ag powder was active above 473 K with reaction orders of unity for O2 and zero for H2CO. All the supported Ag catalysts were active, even below 473 K, but significant deactivation occurred initially at the lower temperatures. Above 473 K the reaction orders for the supported Ag catalysts were near 0.3 for both O2 and H2CO. Turnover frequencies were determined for these Ag catalysts for the first time. Unlike silica, the (HSA) α-aluminas exhibited significant activity above 473 K. In addition to CO2, CO was also a product above 493 K in the presence of alumina, probably due to the decomposition of formate species on the alumina surfaces. The IR spectra for H2CO adsorption on alumina showed that formate groups dominated while significant amounts of dioxymethylene also existed at 303 K. At higher temperatures, dioxymethylene decomposed or oxidized to form formate groups. The spectra for H2CO adsorption on a (HSA) α-alumina-supported Ag catalyst were similar to those for alumina, but a decrease in the formate species was observed after introducing oxygen at 493 K. Formate species were observed on the silica-supported Ag catalyst and were associated with H2CO adsorption on oxygen-covered Ag; introduction of O2 at 493 K after dosing with H2CO resulted in the formation of gas-phase CO2. A reaction model that assumes O2 adsorption and formate decomposition to CO2 to be the two slow steps provided excellent fits for the data for all catalysts.
Protein-translocating trimeric autotransporters of gram-negative bacteria.

Gram-negative bacteria possess a two-membrane envelope with an outer lipopolysaccharide-containing membrane that provides an effective barrier, protecting these organisms from detergents, organic solvents, drugs, and other toxic substances ([24][1]). However, the occurrence of an outer membrane
The role of 4,5-dioxovaleric acid in porphyrin and vitamin B12 formation by clostridia

Abstract 4,5-Dioxovalerate, which has been proposed as an intermediate in the newly discovered so-called C 5 pathway that leads from L-glutamate to δ-aminolevulinate, strongly inhibits uroporphyrin formation from δ-aminolevulinate in cells of Clostridium tetanomorphum and in cell-free extracts of this organism, in spite of the presence of L-alanine: 4,5-dioxovalerate aminotransferase (aminolevulinate aminotransferase, EC 2.6.1.43). The interference by 4,5-dioxovalerate with porphyrin formation is due to strong inhibition of δ-aminolevulinate dehydratase (EC 4.2.1.24). Since 4,5-dioxovalerate hence effectively prevents the operation of the reaction sequence from L-glutamate to porphyrin, it is concluded that 4,5-dioxovalerate does not function as a physiological δ-aminolevulinate precursor.
The Changing Face of Racial Discrimination: Hispanics as the Dominant Minority in the USA - a New Application of Power-Threat Theory:

According to Hubert Blalock’s 1967 power-threat theory, the larger the minority group’s size the greater the threat to the majority group. Most of Blalock’s examples, and much of the subsequent empirical investigation into the power-threat thesis, focus on Anglo and African American relations. Changing demographics will likely alter existing majority-minority relations as Hispanics displace African Americans as the largest minority. This will change the face of racial discrimination in the country. Indeed, this paper suggests that the animosity toward Latinos by both the majority white and minority black populations may be more intense than those shaping contemporary white-black relations. Two key lifestyle features that have not contaminated black-white relations may exacerbate hostility toward Hispanics: their perceived illegal status in the country, and the perception that Hispanics resist learning English. The role of the media in perpetuating these stereotypes and inflaming hostility toward Latinos i...
Technical Note-On Partitioning the Feasible Set in a Branch-and-Bound Algorithm for the Asymmetric Traveling-Salesman Problem

This note develops a branching scheme for a branch-and-bound algorithm for the traveling-salesman problem. It improves on the algorithm of Bellmore and Malone in that a partition of the feasible set is achieved at every vertex of the enumeration tree.
Source location of the smooth high‐frequency radio emissions from Uranus

The source location of the smooth high-frequency radio emissions from Uranus has been determined. Specifically, by fitting the signal dropouts which occurred as Voyager traversed the hollow center of the emission pattern to a symmetrical cone centered on the source magnetic field direction at the cyclotron frequency, a southern-hemisphere (nightside) source was found at approximately 56 deg S, 219 deg W. The half-angle for the hollow portion of the emission pattern was found to be 13 deg.
A DEAD-box protein functions as an ATP-dependent RNA chaperone in group I intron splicing

The Neurospora crassa CYT-18 protein, the mitochondrial tyrosyl-tRNA synthetase, functions in splicing group I introns by inducing formation of the catalytically active RNA structure. Here, we identified a DEAD-box protein (CYT-19) that functions in concert with CYT-18 to promote group I intron splicing in vivo and vitro. CYT-19 does not bind specifically to group I intron RNAs and instead functions as an ATP-dependent RNA chaperone to destabilize nonnative RNA structures that constitute kinetic traps in the CYT-18-assisted RNA-folding pathway. Our results demonstrate that a DExH/D-box protein has a specific, physiologically relevant chaperone function in the folding of a natural RNA substrate.
Correspondence: Response to "Are Complete K-Trees Something More than Decision Trees?"

This is a response to the Correspondence from Gabriel Valiente regarding the article "Using Complete K-Trees to Generate Code in Pascal for an Expert System" that appeared in Volume 1 Number 2 of the SIGART Bulletin. Contrary to his assertion that the idea of a complete K-Tree is the central result presented, as the title indicates, the central result is the use of K-Trees to generate high level code for expert systems. Generation of such code is becoming increasingly important as expert systems, or what many people refer to as expert systems, are being integrated into larger applications. We would, nevertheless, like to clarify some of the points made in the Correspondence.
On topologically equivalent dendrograms

An integral part of clustering is the study of goodness of fit of the clustering imposed by a method on a set of objects. Many measures were introduced to achieve this ([1], [2]). In order to perform hypothesis testing on this measures, we need to know their distributions. To This end, we examine the case of hierarchical clustering, calculate the number of classes of topologically equivalent dendrograms and present two algorithms for finding representatives from each class.
Setup time reduction and competitive advantage in a closed manufacturing cell

Abstract The relationship between setup time reduction and performance improvement in the stochastic closed manufacturing cell is addressed. The improved cell performance is linked with the potential competitive advantage of the firm in the marketplace. An M/G/1 queueing model of a ‘closed manufacturing cell’ (i.e., the cell produces to stock rather than to order) is formulated. Decreasing marginal improvements in cell flow time are shown to result from job setup time reductions. Additionally, marginal reductions in optimal product batch sizes and flow time variance are also shown to diminish as job setup time decreases. Suggestions are provided for allocating limited capital among heterogeneous products for setup time reduction purposes. For given product mix, optimal allocation of setup time reduction investment is shown to be dependent on key product and production parameters.
Comparison of Glargine Insulin Versus Rosiglitazone Addition in Poorly Controlled Type 2 Diabetic Patients on Metformin Plus Sulfonylurea

OBJECTIVE —We sought to examine the mechanisms by which the addition of glargine insulin or rosiglitazone improves glycemic control in type 2 diabetic subjects poorly controlled on maximally effective doses of metformin plus sulfonylurea. RESEARCH DESIGN AND METHODS —Subjects (aged 47 ± 11 years, BMI 31 ± 5 kg/m2, HbA1c [A1C] 9.4 ± 1.3%) received bedtime glargine insulin (titrated based on the fasting plasma glucose [FPG], n = 10) or rosiglitazone (4 mg twice daily, n = 10). At baseline and after 4 months, A1C was measured and an oral glucose tolerance test and a 3-h euglycemic insulin (80 mU/m2 per min) clamp with [3-3H]glucose were performed. RESULTS —A1C and FPG decreased similarly in the glargine insulin (9.1 ± 0.4 to 7.6 ± 0.3% and 212 ± 14 to 139 ± 5 mg/dl, respectively, both P < 0.0001) and rosiglitazone (9.4 ± 0.3 to 7.6 ± 0.4% and 223 ± 14 to 160 ± 19 mg/dl, respectively, both P < 0.005) groups. After 4 months, endogenous glucose production (EGP) declined similarly with glargine insulin (2.27 ± 0.10 to 1.73 ± 0.12 mg · kg−1 · min−1, P < 0.0001) and rosiglitazone (2.21 ± 0.12 to 1.88 ± 0.12 mg · kg−1 · min−1, P = 0.01). The hepatic insulin resistance index declined in the rosiglitazone group (32 ± 3 to 21 ± 1 mg · kg−1 · min−1 × μU/ml, P = 0.03 vs. baseline and P < 0.05 vs. glargine insulin) and did not change in the glargine group (22 ± 5 to 20 ± 3 mg · kg−1 · min−1 × μU/ml, P = NS). At 4 months, glargine insulin (3.6 ± 0.5 to 4.2 ± 0.4 mg · kg−1 · min−1, P < 0.01) and rosiglitazone (2.7 ± 0.3 to 3.8 ± 0.3 mg · kg−1 · min−1, P < 0.0005) increased R d, but the increment was greater in the rosiglitazone group ( P < 0.05). Diastolic blood pressure was reduced only by rosiglitazone ( P < 0.01). CONCLUSIONS —Triple therapy with glargine insulin or rosiglitazone similarly reduced A1C, primarily by suppressing basal EGP (hepatic). Glargine insulin reduced basal EGP by increasing plasma insulin levels, while rosiglitazone decreased basal hepatic glucose production by improving hepatic insulin sensitivity.
Apical cochlear nerve exposed to perilymph in the gerbil and rat.

Abstract There is considerable controversy regarding the origin and composition of perilymph in the scala vestibuli and scala tympani and the barriers and transport mechanisms between them. To elucidate the anatomical separation between perilymph and the extracellular fluid which surrounds the cochlear nerve in Mongolian gerbils (Meriones unguiculatus) and Sprague Dawley rats (Rattus rattus) we examined the modiolus, osseous spiral lamina and the bone of the perilymphatic scalae using light and electron microscopy. Although the cochlear nerve, spiral ganglion and their extracellular fluid are separated from perilymph by the bone of the modiolus in the middle and basal turns, no bone separates these neural structures from perilymph in the apical turn in the two species examined. Instead, the spiral ganglion and axonal elements of the apical turn were covered by a continuation of the bone lining cell layer of the scala tympani. Gaps between lining cells appeared to provide direct communication between the perilymphatic fluid and the extracellular fluid investing the cochlear nerve. Various authors have described openings in modiolar bone in both the scala vestibuli and the scala tympani. While the bone and cellular covering of the modiolus in the basal middle turns of the cochlea is not presumed to be a complete barrier to fluid exchange between the two scalac and the modiolar canal it can be expected to impose some limitation on the rate of passive diffusion. Therefore our data indicates that in the apical turn of the Mongolian gerbil and Sprague-Dawley rat there may be a more significant communication between perilymph and the extracellular fluid and neural elements of the apical modiolar canal than previously reported.
The absorption and distribution of SR-85 by field grown Glycine max

Abstract Introduction Contamination of crops and cropland by fission products as a result of fallout from nuclear explosions and waste from nuclear reactors is a matter of concern. It has been shown (4, 5) that the fission elements yttrium, cerium, zirconium, columbium, tellurium and strontium are absorbed from the soil and translocated in plants only to a limited extent. Of these elements, strontium is absorbed and translocated to the greatest extent. The other elements are apparently more strongly bound to the soil colloid.
Optimizing oral absorption of peptides using prodrug strategies.

Abstract Prodrug strategies applied to peptides have tended to focus on modification of a single functional group (e.g., N-terminal end). Recently, our laboratory introduced the concept of making cyclic prodrugs of peptides as a way to modify their physicochemical properties sufficiently to allow them to permeate biological barriers (i.e., intestinal mucosa). This cyclization strategy required the development of new ‘chemical linkers,’ including an acyloxyalkoxy linker, a phenylpropionic acid linker, and a coumarinic acid linker. All three chemical linkers were designed to be susceptible to esterase metabolism (slow step), leading to a cascade of chemical reactions (fast steps) that result in release of the peptide. These cyclic prodrug strategies have been applied to opioid peptides in an attempt to stabilize them to metabolism and/or improve their intestinal mucosal permeation. Specifically, we prepared acyloxyalkoxy-, phenylpropionic acid- and coumarinic acid-based cyclic prodrugs of [Leu5]-enkephalin (H-Tyr-Gly-Gly-Phe-Leu-OH) and its metabolically stable analog DADLE (H-Tyr- d -Ala-Gly-Phe- d -Leu-OH) and determined their metabolic and biopharmaceutical properties. The cyclic prodrugs of these opioid peptides were shown to have: (i) favorable physicochemical properties (e.g., increased lipophilicity) for membrane permeation; (ii) unique solution structures (e.g., β-turns) that reduce their hydrogen bonding potential; and (iii) metabolic stability to exo- and endopeptidases. The cell membrane permeation characteristics of [Leu5]-enkephalin, DADLE and the cyclic peptide prodrugs were evaluated using Caco-2 cell monolayers, a cell culture model of the intestinal mucosa. The phenylpropionic acid- and coumarinic acid-based cyclic prodrugs of [Leu5]-enkephalin and DADLE were shown to have significantly better cell permeation characteristics than the parent opioid peptides. Furthermore, these cyclic prodrugs were shown to be transcellular permeants (in contrast to the opioid peptides, which are paracellular permeants), and were not substrates for polarized efflux systems. Surprisingly, the acyloxyalkoxy-based prodrugs of [Leu5]-enkephalin and DADLE were shown to exhibit very low permeation through Caco-2 cell monolayers, which could be attributed to their substrate activity for efflux systems.
Comparative study of monolayers self-assembled from alkylisocyanides and alkanethiols on polycrystalline Pt substrates.

This paper compares the properties of self-assembled monolayers (SAMs) derived from octadecylisocyanide (ODI) and octadecanethiol (ODT) on polycrystalline Pt substrates. Both monolayers formed at a...
Ventral tegmental area neurons are either excited or inhibited by cocaine’s actions in the peripheral nervous system

Cocaine's multiple pharmacological substrates are ubiquitously present in the peripheral and central nervous system. Thus, upon its administration, cocaine acts in the periphery before directly acting in the brain. We determined whether cocaine alters ventral tegmental area (VTA) neuronal activity via its peripheral actions. In urethane-anesthetized rats, we recorded VTA neuron's responses to intravenous injections of two cocaine analogs: cocaine-hydrochloride (HCl, 0.25 mg/kg), which readily cross the blood-brain barrier (BBB), and cocaine-methiodide (MI, 0.33 mg/kg), which does not cross the BBB. Both cocaine analogs produced sustained changes in discharge rates that began 5 s after the initiation of a 10-s drug infusion. Within the first 90 s post-injection, the magnitudes of neuronal responsiveness of both cocaine analogs were comparable, but later the effects of cocaine-HCl were stronger and persisted longer than those of cocaine-MI. The proportion of neurons responsive to cocaine-HCl was twice that of cocaine-MI (74% and 35%, respectively). Both analogs also differed in their response onsets. Cocaine-MI rarely evoked responses after 1 min, whereas cocaine-HCl continued to evoke responses within 3 min post-injection. VTA neurons were either excited or inhibited by both cocaine analogs. Most units responsive to cocaine-MI, regardless of whether they were excited or inhibited, had electrophysiological characteristics of putative dopamine (DA) neurons. Units inhibited by cocaine-HCl also had characteristics of DA neurons, whereas excited neurons had widely varying action potential durations and discharge rates. Cocaine-MI and cocaine-HCl each produced changes in VTA neuron activity under full DA receptor blockade. However, the duration of inhibition was shortened and the number of excitations increased, and they occurred with an earlier onset during DA receptor blockade. These findings indicate that cocaine acts peripherally with a short latency and alters the activity of VTA neurons before its well-known direct actions in the brain.
Photopolymerization of pigmented thiol–ene systems

Abstract Photopolymerization kinetics and optical properties of pigmented thiol–ene coatings were investigated using photo-DSC, real-time FTIR, colorimetry, and AFM. Pigment has no deleterious effect on the unique ability of thiol–ene systems to photopolymerize in air. When trimethylolpropane tris-(3-mercaptopropionate) is incrementally added to tripropylene glycol diacrylate with and without calcium lithol rubine, a red organic pigment, the photopolymerization rate in nitrogen steadily decreases due to a shift in the polymerization mechanism from an acrylate homopolymerization to a thiol–ene copolymerization. However, the photopolymerization rate of pigmented and non-pigmented systems in air significantly increases with increasing thiol concentration, ultimately reaching a maximum at approximately 35 mole percent trifunctional thiol. The increase in rate is due to chain transfer from the non-reactive peroxy radical to the thiol. Thiol groups reduce oxygen inhibition to a greater degree than standard additives such as N-methyldiethanolamine, N-vinyl pyrrolidinone, and thioether containing trifunctional vinyl esters. For a typical acrylate based pigmented photocurable system, greater than 10 wt% photoinitiator is required to achieve a photopolymerization rate equivalent to a comparable thiol–ene system with 1 wt% photoinitiator in air. AFM and colorimetric data indicate that addition of trifunctional thiol has no deleterious effect on pigment dispersion and may in fact increase dispersion quality.
Detecting a target letter in briefly presented arrays: A confidence rating analysis in terms of a weighted additive effects model

A visual experiment is reported in which Os rated their “confidence” that briefly presented four-letter arrays contained one or more target-letter Fs. Their responses are interpreted as the product of a weighted “additive” combination of partial or “noisy” subjective representations of the four letters in each array.
Mood and Anxiety Symptoms in Psychiatric Inpatients with Autism Spectrum Disorder and Depression

Recent reports suggest that individuals with autism spectrum disorders (ASD) may experience depression at a high frequency, yet few published studies address this issue, especially among adults. In the current investigation, we reviewed features of depression and comorbid traits among depressed inpatients with intellectual disabilities (ID) as a function of ASD. A retrospective chart review was performed for 53 inpatients meeting criteria for depression (13 individuals with ASD and ID and 40 matched individuals with ID but without ASD), all of whom had received a diagnosis of depression at the time of discharge from a specialty psychiatric unit for adults with ID. The depression diagnoses were based on a comprehensive clinical assessment; specific mood and anxiety symptoms were reported by informants at the time of intake using the Mood and Anxiety Semi-Structured (MASS) Interview for Patients with Intellectual Disabilities (Charlot, Deutsch, Hunt, Fletcher, & McIlvane, 2007). Overall, few qualitative differences were detected between the 2 groups. Both depressed inpatient groups had high rates of comorbid anxiety disorders as well as externalizing behaviors. Inpatients with ASD had a total of 2 more symptoms (out of 29 possible symptom items) than their depressed peers without an ASD diagnosis (mean scores of 12.23 and 9.85, respectively). Anxiety disorders were reported in 62% of individuals with ASD and 38% of those without ASD. Antipsychotic medication was prevalent among the patients with ASD and depression. Over 80% of the inpatients with ASD and depression, compared with 49% of the non-ASD group, were treated with these medications.
Weapons systems analysis, part I: System effectiveness

Abstract Often, a weapon system may be approved based on a particular required military capability without due consideration given to other missions which it might or might not be able to perform. This paper puts forward a methodology for the analysis of weapons systems, and examines various criteria and attributes that relate to system effectiveness. Criteria and attributes included are system performance, operational readiness, life cycle costing, design to cost, reliability, availability, maintainability, producibility, operability, capability, adequacy and logistics.
Applications of Ramsey theory

Abstract This paper attempts to show that Ramsey theory really does have useful applications, by presenting four applications from the literature. The applications are from the fields of communications, information retrieval in computer science, and decisionmaking.
Periventricular nodular heterotopia and Williams syndrome

We report here on the first case of a child with bilateral periventricular nodular heterotopia (PNH) and Williams syndrome. Fluorescent in situ hybridization (FISH) analyses demonstrated a deletion of the elastin gene in the Williams syndrome critical region (WSCR). Further mapping by loss of heterozygosity analysis both by microsatellite marker and SNP profiling demonstrated a 1.5 Mb deletion beyond the telomeric end of the typical WSCR. No mutations were identified in the X-linked filamin-A gene (the most common cause of PNH). These findings suggest another dominant PNH disorder along chromosome 7q11.23.
Effects of altering the balance between prolactin and ovarian hormones on initiation of lactation in rabbits.

Recently we reported (Meites and Sgouris, 1953) that the ability of a moderate dose of prolactin to initiate milk secretion in rabbits with well developed mammary glands, could be effectively inhibited if optimal, mammary growth-promoting doses of estrone and progesterone were injected at the same time. In the absence of either one or both of the steroid hormones, this dose of prolactin elicited a good degree of lactation. The present experiment was undertaken to determine the lactational response in rabbits to injections of (a) large doses of prolactin during treatment with a constant but optimal combination of estrone and progesterone for mammary development and (2) a moderate dose of prolactin in the presence of less than optimal amounts of the two steroid hormones. EXPERIMENTAL Thirty-six New Zealand White rabbits, weighing 5 to 6 pounds each, were ovarieetomized and permitted 10 to 14 days recovery to remove the influence of the ovarian hormones.
Colored dissolved organic matter in coastal waters influenced by the Atchafalaya River, USA: effects of an algal bloom

Colored dissolved organic matter (CDOM) optical properties were studied in the northern Gulf of Mexico coastal waters influenced by the Atchafalaya River in July 2005 during a period of low river discharge using both field and satellite ocean color data. Although a general conservative CDOM absorption-salinity relationship between the riverine and oceanic end members were observed, deviations in surface CDOM absorption from this relationship (CDOM loss) and average higher spectral slope S of the log-linearized absorption spectra in comparison to bottom waters suggested photodegradation of surface CDOM. Excess CDOM absorption in bottom waters at many stations were associated with low oxygen or hypoxic conditions suggesting a potential CDOM source due to remineralization of organic matter in the bottom waters. At a few stations anomalously high CDOM absorption could be linked to biological production associated with algal blooms. Absorption spectra of a surface sample at one such station deviated from standard exponential form in the 300-400m UV range probably due to the presence of photo-protective pigments. CDOM derived from the Sea-Viewing Wide Field-of-View Sensor (SeaWiFS) using a regional algorithm provided a synoptic view of surface CDOM variations and the extent of river influences into the northern Gulf of Mexico.
Use of pharmacologic data and computer simulations to design an efficacy trial of intravesical mitomycin C therapy for superficial bladder cancer

Treatment of superficial bladder cancers by intravesical mitomycin C (MMC) chemotherapy gives a varying and incomplete response. Our recent pharmacokinetics and pharmacodynamics studies have shown that treatment effectiveness is limited by drug degradation in acidic urine and by drug dilution due to residual urine volume and urine production. A model was developed to predict drug exposure in tumors in the bladder wall and to correlate drug exposure with antitumor effect. The model is based on the known pharmacokinetic data in patients treated with intravesical chemotherapy, drug-penetration data in the bladder wall of patients undergoing radical cystectomy, and pharmacodynamic data on patient's bladder-tumor chemosensitivity. Computer simulations based on the model were generated. The simulations predicted that changes in treatment parameters would affect the therapeutic outcome in the following rank order: dose>residual volume>urine production>dosing volume>urine pH>dwell time. Tissue exposure could be enhanced by increased dose, complete bladder emptying, reduced fluid intake, use of the minimal dosing volume, and alkalinization of the urine to a neutral pH. Increasing the dwell time from 2 to 4 h gave an insignificant improvement and posed a compliance problem. The selected optimized regimen of a 40-mg dose, no residual volume, 0.62-ml/min urine production, a 20-ml dosing volume, and alkaline urine pH yielded a calculated 8.5-fold increase in tissue exposure over that achieved by the standard regimen, which consisted of a 20-mg dose, 32-ml residual volume, 1.5-ml/min urine production, a 20-ml dosing volume, and acidic urine pH. On the basis of previously established pharmacodynamic data, we hypothesize that the increase in tissue exposure in the optimized treatment would result in a 20% improvement over the standard therapy along with an increase in the recurrence-free rate from 56% to 76% of patients. A phase III efficacy trial comparing the optimized and standard regimens is proposed.
Scale-Space Spectral Representation of Shape

We construct a scale space of shape of closed Riemannian manifolds, equipped with metrics derived from spectral representations and the Hausdorff distance. The representation depends only on the intrinsic geometry of the manifolds, making it robust to pose and articulation. The computation of shape distance involves an optimization problem over the 2^p-element group of all p-bit strings, which is approached with Markov chain Monte Carlo techniques. The methods are applied to cluster surfaces in 3D space.
Assessment of left ventricular function by intensivists using hand-held echocardiography.

Background Bedside transthoracic echocardiography (TTE) provides rapid and noninvasive hemodynamic assessment of critically ill patients but is limited by the immediate availability of experienced sonographers and cardiologists. Methods Forty-four patients in the medical ICU underwent near-simultaneous limited TTE performed by intensivists with minimal training in echocardiography, and a formal TTE that was performed by certified sonographers and was interpreted by experienced echocardiographers. Intensivists, blinded to the patient's diagnosis and the results of the formal TTE, were asked to determine whether left ventricular (LV) function was grossly normal or abnormal and to place LV function into one of the following three categories: 1, normal; 2, mildly to moderately decreased; and 3, severely decreased. Results Using the formal TTE as the "gold standard," intensivists correctly identified normal LV function in 22 of 24 cases (92%) and abnormal LV function in 16 of 20 cases (80%). The κ statistic for the agreement between intensivist and echocardiographer for any abnormality in LV function was 0.72 (95% confidence interval [CI], 0.52 to 0.93; p Conclusions Intensivists were able to estimate LV function with reasonable accuracy using a hand-held unit in the ICU, despite having undergone minimal training in image acquisition and interpretation.
Modulation of morphine antinociception by peripheral [Leu5]enkephalin: a synergistic interaction.

This study determined whether the modulation of morphine antinociception by [Leu5]enkephalin, a compound which does not produce detectable antinociception when given i.p., was additive or synergistic. Co-administration of graded i.p. doses of morphine and [Leu5]enkephalin 20 min before testing resulted in a progressive leftward and parallel displacement of the i.p. morphine dose-response line. The increase in potency produced by i.p. [Leu5]enkephalin, but not the antinociception of i.p. morphine alone, was blocked by i.c.v. ICI 174,864. The data demonstrate strong and dose-related synergism between the two compounds, supporting the view that (a) peripheral administration of [Leu5]enkephalin can modulate morphine antinociception, apparently at the level of the brain and (b) that the interaction between mu and delta opioid agonists is not the result of simple additive action at the same (i.e., mu) receptor. Further evidence is thus provided for the existence of functional mu-delta interactions.
Contemporary Post Surgical Management of Differentiated Thyroid Carcinoma

Risk assessment is the cornerstone of contemporary management of thyroid cancer. Following thyroid surgery, an initial risk assessment of recurrence and disease-specific mortality is made using important intra-operative findings, histologic characteristics of the tumor, molecular profile of the tumor, post-operative serum thyroglobulin and any available cross-sectional imaging studies. This initial risk assessment is used to guide recommendations regarding the need for remnant ablation, external beam irradiation, systemic therapy, degree of TSH suppression, and follow-up disease detection strategy over the first 2 years after initial therapy. While this initial risk stratification provides valuable information, it is a static representation of the patient in the first few weeks post-operatively that does not change over time. Depending on how the patient responds to our initial therapies, the risk of recurrence and death may change significantly during follow-up. In order to account for differences in response to therapy in individual patients and to incorporate the impact of treatment on our initial risk estimates, we recommend a re-stratification of risk at the 2-year point of follow-up. This re-stratification provides an updated risk estimate that can be used to guide ongoing management recommendations including the frequency and intensity of follow-up, degree of ongoing TSH suppression, and need for additional therapies. Ongoing management recommendations must be tailored to realistic, evolving risk estimates that are actively updated during follow-up. By individualizing therapy on the basis of initial and ongoing risk assessments, we can maximize the beneficial effects of aggressive therapy in patients with thyroid cancer who are likely to benefit from it, while minimizing potential complications and side effects in low-risk patients destined to have a full healthy and productive life after minimal therapeutic intervention.
Nuclear export of the E1B 55‐kDa and E4 34‐kDa adenoviral oncoproteins mediated by a rev‐like signal sequence

The E1B 55-kDa and E4 34-kDa oncoproteins of adenovirus type 5 (abbreviated here as E1B-55kD and E4-34kD) promote the export of viral mRNA and inhibit the export of most cellular mRNA species. We show that the intracellular complex containing E1B-55kD and E4-34kD continuously shuttles between the nucleus and the cytoplasm, and may thus serve as a nucleocytoplasmic transporter for viral mRNA. We present evidence that within this complex, it is the E4-34kD protein that directs both nuclear import and nuclear export. E4-34kD contains a functional nuclear export signal similar to corresponding sequences found in the retroviral proteins rev and rex. This sequence element is required for nuclear export of the complex, and it can function autonomously when fused to a carrier protein and microinjected in HeLa cell nuclei. When E4-34kD is expressed alone, a portion of the protein that contains a predicted arginine-rich amphipathic alpha-helical structure mediates nuclear retention of the protein. This retention, however, can be abolished by the association with E1B-55kD or by a specific point mutation within the arginine-rich motif. The export of E4-34kD can be blocked by an HTLV-rex derived competitive inhibitor and overexpressed E4-34kD inhibits rev-mediated transport, suggesting that the export pathways accessed by the adenoviral and retroviral proteins share components. The interplay between two polypeptides as well as the involvement of a dominant nuclear retention domain are novel features that might contribute to the efficiency and regulation of the adenovirus export system.
International environmental agreements among asymmetric nations

This paper generalizes the benchmark model of self-enforcing international environmental agreements (IEAs) by allowing for all possible coalitions of n asymmetric nations. Asymmetries introduce gains from trade in pollution permits, reducing the incentive to deviate from a properly designed agreement. Coalitions are stable when the aggregate payoff to members is greater than the sum of individual payoffs from leaving the coalition. A benefit-cost ratio rule is proposed which distributes any remaining surplus after each coalition member receives their payoff as a non-signatory. Simulations of 20 asymmetric nations illustrate that even when the gains to cooperation are large, IEAs can achieve substantial emissions reductions. For example, when the benefit-cost ratio is one, stable coalitions can result in 47% of the difference between the full and no cooperation outcomes, compared with 5% for symmetric nations. Furthermore, 72% of the global payoff difference is obtained, relative to 9% for symmetry. Copyright 2007, Oxford University Press.
Complementary GaAs junction-gated heterostructure field effect transistor technology

The first circuit results for a new GaAs complementary logic technology are presented. The technology allows for independently optimizable p- and nchannel transistors with junction gates. Excellent loaded gate delays of 179 ps at 1.2 V and 319 ps at 0.8 V have been demonstrated at low power supply voltages. A power-delay product of 8.9 fJ was obtained at 0.8 V.
Does Frege have too many thoughts? A Cantorian problem revisited

standard probabilistic practice of saying that E provides evidence for H just in case P(H|E) > P(H).) Whether one’s resulting credence in the theory of quantum mechanics would be so low that one would reject quantum mechanics would depend on details like one’s prior probability for Theory X. Even with a probability shift in favour of Theory X, one’s credences could still be such that quantum mechanics is judged vastly more probable than Theory X. Just as the observation of the decay can provide evidence for Theory X and against quantum mechanics, the observation that we are in a small civilization can provide evidence for or against various physical theories. For example, consider Theory Y, which predicts that all civilizations are small. The fact that our civilization is small could constitute evidence in favour of Theory Y and against inflationary theory. But depending on such factors as one’s prior probability for Theory Y, one’s credences could still be such that inflationary theory is judged vastly more probable than Theory Y. Thus, that our civilization is small could lead one to decrease one’s credence in inflationary theory, but nevertheless that credence could still be high. The issue we are discussing in the previous paragraph is a general issue about theory comparison in science; if that is the core of Olum’s paper then there is nothing surprising here. It would be surprising if there were a conflict between anthropic reasoning and observation, but Olum’s argument fails to show that this is the case.
Inhibition of the Tyrosinase Oxidation of One Substrate by Another

The catalytic oxidation of catechol by crude preparations of mushroom tyrosinase was studied by a method yielding data on initial reaction velocities. Graphical analysis of the results suggests that an excess of catechol inhibits its own oxidation by a competitive process, thus accounting for the observed optimum in the substrate concentration. However, added phenol, though itself a substrate, inhibits the enzymatic oxidation of catechol by a process that is neither competitive nor non-competitive, but a mixture of the two types. Mechanisms of this inhibition of the enzyme by a second substrate are discussed in exploring the problem of substrate-substrate inhibition.
Influence of fracture statistics on advective transport and implications for geologic repositories

[1] Large-scale (2.5 km by 2.5 km) simulations of fluid flow and solute transport through low-permeability fractured rock are assessed to determine suitability for hosting a nuclear waste repository. Multiple realizations of fracture networks with statistically realistic features are generated according to established methods. A novel continuum method provides a basis for solving flow and simulating particle trajectories through the fracture networks. Classical and fractional advection-dispersion models form the analytic foundation for statistical summaries of the transport of 25,000 conservative particles through the backbone of each network realization. Particle retention in low-velocity fractures, fast transport, and anomalous dispersion are all observed in the simulated plumes. Predictability is addressed by measuring the deviation of individual plumes from their ensemble average, taken over all realizations for each set of fracture network statistics. Fifteen sets of fracture network statistics are examined, ranging from dense networks of relatively short fractures to sparse networks of rather long fractures. Finally, the plume statistics are carefully examined in order to develop recommendations for suitable geologic repositories on the basis of fracture network statistics.
Screening for Neuropathic Characteristics in Failed Back Surgery Syndromes: Challenges for Guiding Treatment

Objective Neuropathic pain screening tools have shown promise in identifying common neuropathic pain characteristics that derive from diverse etiologies (e.g., diabetic peripheral neuropathy, postherpetic neuralgia). However, no prior studies have specifically assessed whether these tools are capable of discerning the underlying pain mechanisms in the vast, heterogeneous group of patients diagnosed with failed back surgery syndrome (FBSS). Design In this clinical observational study, two tests for neuropathic pain characteristics, the Douleur Neuropathique en 4 (DN4) and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) questionnaires, were performed on 43 subjects with FBSS. Subjects underwent physical or neurosensory exam components of the DN4 and LANSS in the region of most severe pain (e.g., axial low back or lower extremities). DN4 and LANSS scores were correlated with clinical history and neurologic exam, pain-related quality of life questionnaires, and compared to an independent assessment of pain distribution. Results The presence of neuropathic characteristics, determined by the DN4 (62% sensitivity, 44% specificity), LANSS (38% sensitivity, 75% specificity; cut-offs of 4 and 12, respectively), or their combination (20% sensitivity, 58% specificity) was associated with higher pain intensity as measured by the visual analog scale (DN4 > 4, P = 0.001; LANSS ≥ 12, P = 0.042), modified Brief Pain Inventory-Short Form (DN4 > 4, P = 0.001; LANSS ≥ 12, P = 0.082), and Neuropathic Pain Symptom Inventory (DN4 > 4, P = 0.001; LANSS ≥ 12, P = 0.001), and greater pain-related functional impairment as measured by the Roland-Morris Disability Questionnaire (DN4 > 4, P = 0.006; LANSS ≥ 12, P = 0.018). The percentage of subjects characterized as neuropathic by the DN4 and LANSS lacked concordance (67.4 vs 25.6), and the distribution of most severe symptoms (i.e., axial vs radicular) did not correlate with subjects determined to have neuropathic pain. Conclusions Unlike other neuropathic syndromes, the neuropathic component of FBSS is less reliably identified by the LANSS and DN4.
Development of monitoring and decision-support systems for integrated pest management of forest defoliators in North America

Abstract The concept of integrated pest management has been accepted by forest pest managers for many years, but its implementation has been hindered by the lack of monitoring systems and decisionmaking tools. Within the last seven years, monitoring systems have been developed which show promise as early-warning systems and for making control decisions. Computer-aided decision-support tools such as models, database management systems, geographic information systems, and expert systems also show promise, but research in the areas of user interfaces and the incorporation of system intelligence is needed. This paper reviews the advances made with monitoring systems and decision-support tools with reference to the major defoliators of North American forests. Research accomplished by the Douglas-fir tussock moth, spruce budworm, and gypsy moth programs is reviewed.
Structural comparison of recombinant human macrophage colony stimulating factor β and a partially reduced derivative using hydrogen deuterium exchange and electrospray ionization mass spectrometry

Hydrogen deuterium exchange, monitored by electrospray ionization mass spectrometry, has been employed to characterize structural features of a derivative of recombinant human macrophage colony stimulating factor beta (rhm-CSF) in which two of the nine disulfide bridges (Cys157/Cys159–Cys157/Cys159) were selectively reduced and alkylated. Removal of these two disulfide bridges did not affect the biological activity of the protein. Similarities between CD and fluorescence spectra for rhm-CSF and its derivative indicate that removing the disulfide bonds did not strongly alter the overall three-dimensional structure of rhm-CSF. However, differences between deuterium exchange data of the intact proteins indicate that more NHs underwent fast deuterium exchange in the derivative than in rhm-CSF. Regions located near the disulfide bond removal site were shown to exhibit faster deuterium exchange behavior in the derivative than in rhm-CSF.