cssi/SciSciGPT-SciSciNet huggingface dataset:
Antitumor agents. 174. 2',3',4',5,6,7-Substituted 2-phenyl-1,8-naphthyridin-4-ones: their synthesis, cytotoxicity, and inhibition of tubulin polymerization.

Two series of 2‘,3‘,4‘,5,6,7-substituted 2-phenyl-1,8-naphthyridin-4-ones and 2-phenylpyrido[1,2-a]pyrimidin-4-ones have been synthesized and evaluated as cytotoxic compounds and as inhibitors of tubulin polymerization. Most 2-phenyl-1,8-naphthyridin-4-ones showed potent cytotoxic and antitubulin activities, whereas 2-phenylpyrido[1,2-a]pyrimidin-4-ones showed no activity in either assay. In general, a good correlation was found between cytotoxicity and inhibition of tubulin polymerization in the 2-phenyl-1,8-naphthyridin-4-one series. The 2-phenyl-1,8-naphthyridin-4-ones (44−49) with a methoxy group at the 3‘-position showed potent cytotoxicity against most tumor cell lines with GI50 values in the low micromolar to nanomolar concentration range in the National Cancer Institute's 60 human tumor cell line in vitro screen. Introduction of substituents (e.g. F, Cl, CH3, and OCH3) at the 4‘-position led to compounds with reduced or little activity and substitution at the 2‘-position resulted in inactive compo...
On quantization errors in computer vision

The author considers the error resulting in the computation of multivariable functions h(X/sub 1/, X, . . ., X/sub n/), where all the X/sub i/s are only available in the quantized form. In image processing and computer vision problems, the variables are typically a mixture of the spatial coordinates and the intensity levels of objects in an image. A method is introduced using a first-order Taylor series expansion together with a periodic extension of the resulting expression and its Fourier series representation so that the moments and the probability distribution function of the error can be computed in closed form. This method only requires that the joint probability density function of X/sub i/s be known and makes no assumption on the behavior on the quantization errors of the variables. Examples are also given where these results are applied. >
Optical Tomography for Variable Refractive Index with Angularly Averaged Measurements

In optical tomography one seeks to use near-infrared light to determine the optical absorption and scattering properties of a medium X ⊂ ℝ n . If the refractive index is constant throughout the med...
Comparison of regional differences in cardiac myocyte dimensions in rats, hamsters, and guinea pigs

Isolated myocytes were prepared from Sprague Dawley rats, golden Syrian hamsters, and Hartley guinea pigs to investigate regional variations in myocyte size. Cell volume (V) was measured with a Coulter Channelyzer, cell length (L) was measured directly, and cross-sectional area (CSA) was calculated from V/L. Compared to values from the left ventricle (LV), right ventricular L was shorter in the rat (P less than .01) and hamster (P less than .05) and longer in the guinea pig (P less than .01). Guinea pig atrial L was shorter (P less than .01) than L in the right ventricle (RV) but did not differ from L in the LV. No significant differences in L existed between endomyocardium, middle myocardium, and epimyocardium of the LV in all three species. In rats and hamsters, myocytes from the RV had smaller V and CSA values (P less than .01) compared to any region of the LV. A transmural gradient of cellular dimensions existed in the LV of the rat, but not in hamster, with V and CSA of endomyocardium being largest and epimyocardium smallest (P less than .01). Endomyocardial V and CSA were larger (P less than .01) than all other regions in the hamster, but the difference was not significant compared to epimyocardial V. In the guinea pig, no significant differences in V existed between RV and LV or between the three LV regions. No pattern of regional differences was seen between ventricular CSA values in the guinea pig. Guinea pig atrial V and CSA values were smaller (P less than .01) than those for ventricular myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Multixenobiotic resistance mechanism in the catfish intestine

Abstract A mechanism similar to the multidrug resistance phenomenon displayed by mammalian tumor cells has been identified in a variety of lower species, and in a variety of tissues, including the gastrointestinal tract. Xenobiotic efflux transport activity, and the location in membranes of the gastrointestinal tract luminal surfaces, indicates that P-glycoprotein (pgp) may act in modulating the bioavailability of dietary xenobiotics in aquatic animals. The objectives of this study were to investigate the dietary inducibility, depuration, and transport abilities of pgp in the catfish intestine. For this purpose, catfish underwent dietary induction with benzo(a)pyrene, β-naphthoflavone, and 3,4,3′,4′-tetrachlorobiphenyl. Plasma membrane vesicles preparations were used for protein quantitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, western blot, and immunohistochemical detection with C219 monoclonal antibody. Transport activity was tested using [3H]-vinblastine (VBL) as a substrate. Results have shown that a catfish intestinal protein which cross-reacts with C219 antibody is inducible following dietary xenobiotic exposure, and that lower levels of this protein are still present 16 days after termination of exposure. In addition, VBL transport was shown to be ATP dependent and inhibited by verapamil. The location, function and responsiveness of pgp to dietary inducers suggest that pgp may play a role in the bioavailability and disposition of dietary xenobiotics.
Review Article: The New Concept of Interventional Heart Failure Therapy—Part 1: Electrical Therapy, Treatment of CAD, Fluid Removal, and Ventricular Support

Congestive heart failure is a chronic and debilitating disease responsible for high cardiac morbidity and mortality in the world and is associated with more than 290 000 deaths in the United States...
Holographic optical switching with photorefractive crystals

A switching technique using the polarization sensitivity of photorefractive holograms in crystals is experimentally demonstrated. The design is capable of handling a large number of 2 X 2 switching channels with only four holograms. The concept is applicable to either synchronous or asynchronous switching and also to a variety of photorefractive materials.
Differential Mechanical Response of Mesenchymal Stem Cells and Fibroblasts to Tumor-Secreted Soluble Factors

The progression of neoplastic malignancies is a complex process resulting not only from the accumulation of mutations within tumor cells, but also modulation of the tumor microenvironment. Recent advances have shown that the recruitment and subsequent heterotypic interactions of stromal cells—including fibroblasts and bone marrow-derived mesenchymal stem cells (MSCs)—are crucial for carcinogenesis. Though extensive work has been done analyzing the signals that recruit these cells, the governing mechanical properties have not been fully investigated. Here, we report that despite their initial similarities, MSCs respond not only faster but also more dramatically to pro-migratory tumor-secreted soluble factors. Utilizing multiple particle tracking microrheology to probe the cytoskeletal mechanical properties, we show that MSCs stiffen completely within one hour, three times faster than fibroblasts. In addition, unlike fibroblasts, MSCs exposed to tumor-secreted soluble factors display a functionally different phenotype characterized by morphological elongation, decreased actin stress fiber density, and decreased adhesion. Quantitative real-time PCR indicates these phenomena occur based on differential expression of small GTPases RhoA and Cdc42, but not Rac1. These findings demonstrate a fundamental difference in the recruitment of fibroblasts and MSCs.
Chemical energy release in the cellular structure of gaseous detonation waves

Abstract The nonequilibrium Zel'dovich-von Neumann-Doring (ZND) model is applied to the three-dimensional cellular structure of ordinary and marginal gaseous detonation waves. Calculations of the nonequilibrium chemical energy release in the chain-propagating reactions of H 2 + Cl 2 at various shock temperatures show that relatively thick zones of highly vibrationally excited reaction products exist at varying distances behind all of the shock fronts in the cellular structure. Therefore, each of these shock fronts is supported to a different extent by the chemical reconstitution process. Calculations for ordinary detonations of H 2 + Cl 2 and 2H 2 + O 2 using a constant transverse wave strength and a simple rigid wall reflection for the transverse wave collision process yield good agreement with experimental cell parameters. The calculations indicate that approximately 1 4 of the energy required for self-sustaining propagation of the leading shock front is furnished by the transverse wave collision process. For a marginal detonation in 2H 2 + O 2 + 3Ar, calculations based on a decreasing transverse wave strength and the recent suggestion of Dormal et al. that the reinitiation process at the end of a cell includes a detonation in the precompressed explosive behind the incident wave agree with experimental measurements. This application of the nonequilibrium ZND model may explain the experimental observation of a cellular structure in an overdriven detonation whose heat of reaction is endothermic and suggest extensions of the Vasil'ev et al. model of a cell in a self-sustaining gaseous detonation wave.
A SIMPLE METHOD FOR CALCULATING THE LINEAR EXTRAPOLATION DISTANCE AT THE SURFACE OF A BLACK BODY

Abstract We adapt a method introduced by Fuchs for calculating evaporation rates from small droplets to the evaluation of the linear extrapolation distance of the neutron density at the surface of a black body immersed in an infinite, absorbing medium. Explicit results are obtained for spheres and cyclinders and, by comparison with some very accurate calculations carried out by others, these results are shown to be accurate to within about 9% for a range of parameters. Modifications are introduced which enable the method to deal with absorbing and scattering bodies which are not black.
Effects of Antioxidant Herbs on Chemotherapy-Induced Nausea and Vomiting in a Rat-Pica Model

Nausea and vomiting are significant adverse effects of chemotherapeutic agents like cisplatin, and cause significant patient morbidity. Cisplatin treatment results in oxidant gut injury, which is postulated to be the primary cause of nausea and vomiting. We evaluated the effects of two antioxidant herbs, Scutellaria baicalensis and American ginseng berry, on cisplatin-induced nausea and vomiting using a rat model. Rats react to emetic or nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by increased kaolin consumption (pica). We measured pica in rats to quantify cisplatin-induced nausea. We observed that pretreatment of rats with S. baicalensis or ginseng berry extracts resulted in a significant reduction in cisplatin-induced pica. The in vitro free radical scavenging ability of the herbal extract observed in the study, further confirmed the antioxidant action of the herb. We conclude that herbal antioxidants may have a role in attenuating cisplatin-induced nausea and vomiting.
Human galanin expresses amphipathic properties that modulate its vasoreactivity in vivo.

Abstract The purpose of this study was to determine whether human galanin, a pleiotropic 30-amino acid neuropeptide, expresses amphipathic properties in vitro and, if so, whether these properties modulate its vasoactive effects in the intact peripheral microcirculation. We found that human galanin aggregates in an aqueous solution and forms micelles with a critical micellar concentration (CMC) of 0.4 μM. In addition, the peptide interacted with model membrane as indicated by long and significant increase of the surface pressure of the biomimetic monolayer membrane in vitro. Interactions of human galanin with sterically stabilized phospholipid micelles (SMM) were not associated with a significant change in peptide conformation. Using intravital microscopy, we found that suffusion of human galanin alone elicited significant concentration-dependent vasoconstriction in the intact hamster cheek pouch. This response was amplified when human galanin in SSM was suffused onto the cheek pouch. The effects of human galanin alone and in SSM were mediated by galanin receptors because galantide, a galanin receptor antagonist, abrogated galanin-induced vasoconstriction. Collectively, these data show that human galanin expresses amphipathic properties in the presence of phospholipids which in turn amplifies its vasoactive effects in the intact peripheral microcirculation.
Movement of coliform bacteria and nutrients in ground water flowing through basalt and sand aquifers

Large-scale deposition of animal manure can result in contamination of surface and ground water and in potential transfer of disease-causing enteric bacteria to animals or humans. We measured total coliform bacteria (TC), fecal coliform bacteria (FC), NO3, NH4, total P, and PO4 in ground water flowing from basalt and sand aquifers, in wells into basalt and sand aquifers, in irrigation water, and in river water. Samples were collected monthly for 1 yr. Total coliform and FC numbers were always higher in irrigation water than in ground water, indicating that soil and sediment filtered most of these bacteria before they entered the aquifers. Total coliform and FC numbers in ground water were generally higher in the faster flowing basalt aquifer than in the sand aquifer, indicating that the slower flow and finer grain size may filter more TC and FC bacteria from water. At least one coliform bacterium/100 mL of water was found in ground water from both basalt and sand aquifers, indicating that ground water pumped from these aquifers is not necessarily safe for human consumption according to the American Public Health Association and the USEPA. The NO3 concentrations were usually higher in water flowing from the sand aquifer than in water flowing from the basalt aquifer or in perched water tables in the basalt aquifer. The PO4 concentrations were usually higher in water flowing from the basalt aquifer than in water flowing from the sand aquifer. The main concern is fecal contamination of these aquifers and health consequences that may arise from human consumption.
Individual Social-Cognitive Intervention for Aggressive Behavior in Early Adolescence An Application of the Cognitive-Ecological Framework

This study presents a case of successful treatment provided to an early-adolescent African American male diagnosed with conduct disorder. Treatment in this case was conceptualized using a cognitive...
A comparison of the fungicidal activity of amphotericin B and posaconazole against Zygomycetes in vitro

Zygomycoses is a rapidly progressive infection associated with high mortality. Although amphotericin B (AMB) has been the only treatment option for years, recent studies have demonstrated that posaconazole (PCZ) has good activity against Zygomycetes. Because rapid onset of antifungal activity is crucial in the management and never studied before, we compared the time for maximum fungicidal activity of AMB versus PCZ using time-kill curves. The MIC of AMB and PCZ against clinical isolates of Mucor spp. and Rhizopus spp. was determined by the Clinical and Laboratory Standards Institute M38-A2 method, and the fungicidal activity was examined by time-kill studies. AMB was rapidly fungicidal, with 95% killing noted as early as 6 h and 99.9% killing at 24 h; PCZ showed <70% killing at 6 h and 99.9% killing at 48 h. In vivo animal studies using AMB in the early phase, followed by a switch to high-dose PCZ later, could provide data that may have clinical implications because there are only a few drugs currently available for the management of zygomycoses.
Young Children's Meaning in Life:

Summary.-A decade ago DeVogler and Ebersole reported that young adolescents were able to express the fact that they had personal meaning in their lives. In the present study we found that even younger children (26 first graders) could do so also when personal meaning was defined to them as that which in their whole life is most important to them. The high frequency of those reporting a personal meaning goes against the position that a large percentage of individuals in our modern society lack personal meaning. Investigations of meaning in life have focused almost entirely on college students and older adults perhaps because researchers presumed that the psychological complexity implied in the development of a life meaning only could be achieved by mature human beings. A decade ago DeVogler and Ebersole (1983) challenged this assumption by demonstrating that young adolescents were fully as capable as adults of producing viable statements about the meaning in their lives. Their eighth-grade participants were able to write clearly in some depth about their life meanings "without any obvious fundamental deviation" (p. 429) from how older samples approached the question of their life meaning. In comparing these adolescents to college-student samples with which they were familiar, DeVogler and Ebersole concluded, "The huge majority of expressions in both groups seemed substantively interchangeable except for varying degrees of elaboration and sophistication of expression" (p. 430). What about yet younger children, children just beginning their schooling? Could even they, as young as they are, have already developed a life meaning? The present study was designed to answer this question. The methodology DeVogler and Ebersole (1983) had employed to study the adolescents' meaning in life was the same as that for adults (e.g., DeVogler & Ebersole, 1981): they were asked to write about their personal life meaning. In the present study, our first graders' lack of writing skills precluded us from studying them in a manner exactly like that of the older ones, but we still could examine the presence or absence of the younger children's meanings by asking them to respond verbally to our questioning. A second methodological obstacle was the possibility that such young children might be unable to comprehend what is being asked of them when requested to discuss their personal life meaning. We adjusted for that by putting our central ques
Microendoscopic decompression for cervical spondylotic myelopathy

Object Cervical spondylotic myelopathy (CSM) is a common cervical degenerative disease that affects the elderly population. Spinal cord decompression is achieved through various anterior and posterior approaches including anterior cervical decompression and fusion, laminectomy, laminoplasty, and combined approaches. The authors describe another option, minimally invasive endoscopically assisted decompression of stenosis (MEDS), which obviates the need for muscle dissection and disruption of the posterior tension band, a cause of postlaminectomy kyphosis. Methods The authors conducted a retrospective study of 10 patients with CSM who underwent MEDS from January 2002 through July 2012. Data were collected on demographics, preoperative and postoperative Nurick scores, postoperative Odom scores, and preoperative and postoperative Cobb angles. Results The mean patient age (± SD) was 67 ± 7.7 years; 8 patients were male. The average number of disc levels operated on was 2.2 (range 1–4). The mean Nurick score wa...
Disorder-induced depression of the Curie temperature in mechanically milled Gd Al 2

The effect of disorder on the ferromagnetic transition is investigated in mechanically milled $\mathrm{Gd}{\mathrm{Al}}_{2}$. $\mathrm{Gd}{\mathrm{Al}}_{2}$ is a ferromagnet when crystalline and a spin glass when amorphous. Mechanical milling progressively disorders the alloy, allowing observation of the change from ferromagnetic to a disordered magnetic state. X-ray diffraction and pair-distribution-function analysis are used to determine the grain size, lattice parameter, and mean-squared atomic displacements. The magnetization as a function of temperature is described by a Gaussian distribution of Curie temperatures. The mean Curie temperature decreases with decreasing lattice parameter, where lattice parameter serves as a measure of defect concentration. Two different rates of change with lattice parameter are observed: the first, slower rate occurs while grain size is changing, and the grain size is constant in the second regime. The breadth of the Curie temperature distribution is linear with lattice parameter. Milled and annealed $\mathrm{Gd}{\mathrm{Al}}_{2}$ shows that the mean Curie temperature has the same general dependence on lattice parameter as milled, but unannealed $\mathrm{Gd}{\mathrm{Al}}_{2}$, while the breadth of the Curie temperature distribution is different in annealed samples compared to the unannealed materials.
Cell biology of infection by Legionella pneumophila

Professional phagocytes digest internalized microorganisms by actively delivering them into the phagolysosomal compartment. Intravacuolar bacterial pathogens have evolved a variety of effective strategies to bypass the default pathway of phagosomal maturation to create a niche permissive for their survival and propagation. Here we discuss recent progress in our understanding of the sophisticated mechanisms used by Legionella pneumophila to survive in phagocytes.
Underwater multi-view three-dimensional imaging with passive sensing

In this keynote address paper, an overview of multi-view three-dimensional (3D) imaging with passive sensing for underwater applications is presented. The 3D Synthetic Aperture Integral Imaging (SAII) technique is adapted for underwater sensing. The change in apparent object distance caused by the refractive index of water must be accounted for in computational 3D image reconstructions. An experimental environment with objects in water and SAII system in air or water is presented. Experimental results are presented to demonstrate the ability of the underwater 3D SAII system.
School violence: issues of teacher voice and domination

While politicians and the media have devoted a great deal of attention to the "problem" of school violence, classrooms teachers remain an underutilized source of information and inspiration about the frequency of school violence, its causes, its consequences, and appropriate interventions. In essence, teachers have been given little, if any, voice. This article is a reflective piece that integrates the author's own experiences as a teacher, focus group data with high school teachers, and the extant literature regarding the importance of teacher voice. Research and theory regarding the relationship between the colonizer and the colonized serve as background. Also explored are the ways that teachers' voices are stifled, as well as suggestions for empowering teachers.
Neocortical Dendritic Pathology in Human Partial Epilepsy: A Quantitative Golgi Study

We used a computerized image-analysis system to perform a quantitative analysis of rapid Golgi-impregnated pyramidal neurons of the third cortical layer of histologically normal cerebral cortex surgically removed from patients with partial epilepsy. Various parameters of 51 neurons from 9 patients and 29 neurons from 5 age-matched controls were compared. Dendritic spine density decreased progressively with increasing duration of seizures, and dendritic swellings were most numerous in epilepsy cases of uncertain etiology and in patients with seizures of longer standing. Neurons from seizure cases showed fewer dendritic branching points and fewer proximal dendritic branches than those from controls, suggesting a simplified dendritic architecture. These findings indicate that neurons in cortex distant from the primary site of epileptogenic activity may be undergoing subtle, progressive degeneration, which may explain the propensity of chronic epilepsy patients to have increased seizure activity and interictal behavioral and cognitive aberrations.
On the length formula of Hoskin and Deligne and associated graded rings of two-dimensional regular local rings

Let (R, m) be a 2-dimensional regular local ring and I an m-primary ideal. The aim of this paper is to find conditions on I so that the associated graded ring of I,and the Rees ring of I,where t is an indeterminate, are Cohen–Macaulay (resp. Gorenstein). To this end, we use the results and techniques from Zariski's theory of complete ideals ([14], appendix 5) and its later generalizations and refinements due to Huneke [7] and Lipman[8]. The main result is an application of three deep theorems: (i) a generalization of Macaulay's classical theorem on Hilbert series of Gorenstein graded rings [13], (ii) a generalization of the Briancon–Skoda theorem due to Lipman and Sathaye [9], and (iii) a formula for the length of R/I, where I is a complete m-primary ideal, due to Hoskin[4] and Deligne[1].
Consideration of hereditary nonpolyposis colorectal cancer in BRCA mutation‐negative familial ovarian cancers

BACKGROUND: Inherited mutations account for approximately 10% of all epithelial ovarian cancers. Breast cancer (BRCA1 and BRACA2) gene mutations are responsible for up to 85% of inherited breast and/or ovarian cancer. Another condition that has been associated with ovarian cancer is hereditary nonpolyposis colorectal cancer syndrome (HNPCC), which carries a lifetime risk of up to 13% for ovarian cancer. The objective of this study was to determine the incidence of HNPCC-related gene mutations in patients with familial ovarian cancer who previously tested negative for BRCA1 and BRCA2 gene mutations. METHODS: Seventy-seven probands were identified who had familial ovarian cancer and negative BRCA gene mutation testing. Their pedigrees were analyzed for HNPCC syndrome. DNA samples underwent gene sequencing and Southern blot analysis for mutations in the 3 most common HNPCC-associated genes: mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2) with reflex testing for MSH6 if tests for the first 2 genes were negative. RESULTS: None of the probands met Amsterdam criteria for the clinical diagnosis of HNPCC. DNA testing revealed 2 patients (2.6%) with deleterious mutations in the MSH2 gene. An additional 8 patients (10.4%) had substitutions in either the MLH1 gene or the MSH2 gene that were classified as variants of uncertain significance. If Amsterdam criteria were expanded to include ovarian cancer, then 15 of 77 patients (19.5%) would have met these expanded criteria. One deleterious mutation was noted in this group, yielding a mutation incidence of 6.7%. This percentage may be even higher if any of the identified variants of uncertain significance are confirmed to be deleterious. CONCLUSIONS: HNPCC should be considered when evaluating patients with suspected hereditary ovarian cancer who have had negative BRCA mutation testing. Cancer 2009. © 2009 American Cancer Society.
Off-Stream Detention Design for Storm-Water Management

AbstractA detention basin is designed for storm-water quantity and quality controls. An in-stream basin is often located on a widened floodplain, whereas an off-stream basin can be part of open space in a parking lot, park, or sport field. The inflow channel associated with an off-stream basin is allowed to carry its base flow not to exceed the downstream capacity. When the inflow channel is full, the excess flood water is diverted into the off-stream basin through the side weir. During the flood recession, the equalizer conduit drains the basin flow back to the channel. In this study, the rational volumetric method was expanded from in-stream to off-stream detention design. The required off-stream detention volume is maximized by the rainfall event longer than the time of concentration of the tributary area. In comparison, the off-stream detention volume can be significantly less than an in-stream, depending on the flow-through capacity in the downstream channel. This paper presents a design procedure to...
Kinetic, spectroscopic, and theoretical assessment of associative and dissociative methanol dehydration routes in zeolites.

Mechanistic interpretations of rates and in situ IR spectra combined with density functionals that account for van der Waals interactions of intermediates and transition states within confining voids show that associative routes mediate the formation of dimethyl ether from methanol on zeolitic acids at the temperatures and pressures of practical dehydration catalysis. Methoxy-mediated dissociative routes become prevalent at higher temperatures and lower pressures, because they involve smaller transition states with higher enthalpy, but also higher entropy, than those in associative routes. These enthalpy–entropy trade-offs merely reflect the intervening role of temperature in activation free energies and the prevalence of more complex transition states at low temperatures and high pressures. This work provides a foundation for further inquiry into the contributions of H-bonded methanol and methoxy species in homologation and hydrocarbon synthesis reactions from methanol.
Data Bus Inversion in High-Speed Memory Applications

Efforts to reduce high-speed memory interface power have led to the adoption of data bus inversion or bus-invert coding. This study compares two popular algorithms, which seek to limit the number of simultaneously transitioning signals and bias the state of transmitted data toward a preferred binary level, respectively. A new algorithm, which provides a compromise between transition frequency and preferred signal level, is proposed, and the three algorithms are compared in terms of their impact on power consumption, power supply noise reduction, and general signal integrity enhancement when used in conjunction with a variety of link topologies.
Molecular analysis of mutS expression and mutation in natural isolates of pathogenic Escherichia coli.

Deficiencies in the MutS protein disrupt methyl-directed mismatch repair (MMR), generating a mutator phenotype typified by high mutation rates and promiscuous recombination. How such deficiencies might arise in the natural environment was determined by analysing pathogenic strains of Escherichia coli. Quantitative Western immunoblotting showed that the amount of MutS in a wild-type strain of the enterohaemorrhagic pathogen E. coli O157 : H7 decreased about 26-fold in stationary-phase cells as compared with the amount present during exponential-phase growth. The depletion of MutS in O157 : H7 is significantly greater than that observed for a laboratory-attenuated E. coli K-12 strain. In the case of stable mutators, mutS defects in strains identified among natural isolates were analysed, including two E. coli O157 : H7 strains, a diarrhoeagenic E. coli O55 : H7 strain, and a uropathogenic strain from the E. coli reference (ECOR) collection. No MutS could be detected in the four strains by Western immunoblot analyses. RNase T2 protection assays showed that the strains were either deficient in mutS transcripts or produced transcripts truncated at the 3' end. Nucleotide sequence analysis revealed extensive deletions in the mutS region of three strains, ranging from 7.5 to 17.3 kb relative to E. coli K-12 sequence, while the ECOR mutator contained a premature stop codon in addition to other nucleotide changes in the mutS coding sequence. These results provide insights into the status of the mutS gene and its product in pathogenic strains of E. coli.
Cocaine-induced locomotor sensitization in rats correlates with nucleus accumbens activity on manganese-enhanced MRI

A long-standing goal of substance abuse research has been to link drug-induced behavioral outcomes with the activity of specific brain regions to understand the neurobiology of addiction behaviors and to search for drug-able targets. Here, we tested the hypothesis that cocaine produces locomotor (behavioral) sensitization that correlates with increased calcium channel-mediated neuroactivity in brain regions linked with drug addiction, such as the nucleus accumbens (NAC), anterior striatum (AST) and hippocampus, as measured using manganese-enhanced MRI (MEMRI). Rats were treated with cocaine for 5 days, followed by a 2-day drug-free period. The following day, locomotor sensitization was quantified as a metric of cocaine-induced neuroplasticity in the presence of manganese. Immediately following behavioral testing, rats were examined for changes in calcium channel-mediated neuronal activity in the NAC, AST, hippocampus and temporalis muscle, which was associated with behavioral sensitization using MEMRI. Cocaine significantly increased locomotor activity and produced behavioral sensitization compared with saline treatment of control rats. A significant increase in MEMRI signal intensity was determined in the NAC, but not AST or hippocampus, of cocaine-treated rats compared with saline-treated control rats. Cocaine did not increase signal intensity in the temporalis muscle. Notably, in support of our hypothesis, behavior was significantly and positively correlated with MEMRI signal intensity in the NAC. As neuronal uptake of manganese is regulated by calcium channels, these results indicate that MEMRI is a powerful research tool to study neuronal activity in freely behaving animals and to guide new calcium channel-based therapies for the treatment of cocaine abuse and dependence.
NUMERICAL SIMULATION OF A FILM-COOLED LOX/RP-1 ROCKET NOZZLE

Numerical simulations were made to evaluate film-cooling strategies for cooling the throat of the NASA Fast Track chamber. Film-cooling through an injector face port and in combination with an additional port between the injector and throat were considered. The gaseous LOX/RP-1 thrust chamber was simulated with the CFD-ACE code which uses an implicit, pressure-based, finite-volume, hybrid upwind scheme to solve the Favre-averaged Navier-Stokes equations and the species equations. A reduced set of chemical species was developed to model the equilibrium chemistry of LOX/RP-1. Results show that it is possible to optimize the distribution of filmcoolant between the injector and the additional coolant port to maintain the nozzle wall temperature below the 3600°R threshold temperature required to maintain the nozzle liner ablation rate below 2 mils/s. The simulations confirm that the cooling effectiveness of RP-1 is due to a highly endothermic cracking process. A conjugate gradient heat transfer analysis indicates that the additional coolant port would probably have to be manufactured out of a material other than pure copper. Finally, both film-cooling approaches only decreased the nozzle specific impulse by 2%.
Laparoscopic salvage of malfunctioning peritoneal catheters.

Background: Malfunction of peritoneal catheters due to mechanical outflow problems is an annoying complication in patients undergoing chronic peritoneal dialysis (PD). Correction often involves catheter replacement or revision via laparotomy.
Polarization-instability and performance of free-space optical links based on vertical-cavity surface-emitting lasers

We show here that the polarization instability results in signal-to-noise ratio (SNR) degradation and the appearance of bit error-rate (BER) floors in polarization-sensitive optical links. This limits performance of vertical cavity surface emitting laser [VCSEL-based] free-space optical interconnects to data rates significantly lower than the laser modulation bandwith. In conclusion, our experiments suggest that in the absence of polarization stability, data transmission rates in polarization-sensitive links based on VCSELs will be limited to -300 Mb/s.
Risk factors for local recurrence in patients with invasive breast cancer and negative surgical margins of excision. Where are we and where are we going

The results of 6 prospective randomized clinical trials have clearly demonstrated that the combination of breastconserving surgery (CS) and radiation therapy (RT) provides survival rates equivalent to those observed following mastectomy. 1 Consequently, the CS-RT combination is now a standard therapeutic option for the treatment of many women with early-stage invasive breast cancer and is preferable to mastectomy because of the cosmetic benefit of breast preservation. 2 Although the CS-RT combination generally is associated with a high level of local tumor control, a recurrence develops in the treated breast in a small proportion of patients (approximately 1.0%-1.5% per year). 3 While the impact of such local recurrences on survival remains a matter of debate, 4 minimizing the risk of local recurrence in patients choosing breast-conserving therapy remains an important clinical objective. Numerous studies have indicated that most local recurrences following treatment with CS and RT are in the mammary parenchyma, at or near the primary tumor site, and that local recurrence rates are lower when a wider resection of the tumor is performed. Taken together, these observations suggest that an “adequate” excision of the primary tumor is necessary to obtain optimal local tumor control. Efforts to determine what constitutes an adequate excision before RT have focused on the identification of risk factors for local recurrence. Although a variety of clinical, treatment, and pathologic factors have been reported to be associated with an increased risk of local recurrence following CS and RT, 3 the status of the final microscopic margins of excision is among the most important of these in daily clinical practice. The technical limitations in assessing microscopic
Biophysical Factors, Land Use, and Species Viability in and around Nature Reserves

Many nature reserves are located in landscapes with extreme biophysical conditions. We examined the effects of interactions between biophysical factors and land use on bird population viability inside and out- side of Yellowstone National Park. Our hypotheses were as follows: (1) biophysical factors constrain bird species richness and bird reproduction at higher elevations; (2) nature reserves are located at higher elevations, whereas private lands and more intense land use occur mostly at lower elevations with more mild climates and fertile soils; and (3) intense land use at lower elevations favors nest predators and brood parasites and thereby re- duces reproductive output for some bird species. We used simulation models to evaluate whether favorable hab- itats outside reserves are population source areas and whether intense land use can convert these habitats to population sinks and reduce population viability within reserves. Bird species richness and abundance were high in small hotspots in productive, low-elevation habitats. Length of breeding season—and opportunity for renesting—was greatest at the lowest elevations for both American Robins ( Turdus migratorius ) and Yellow Warblers ( Dendroica petechia ). Nature reserves were higher in elevation than private lands, so hotspots for bird richness and abundance occurred primarily on or near private lands, where rural residential development was concentrated. Brown-headed Cowbirds ( Molothrus ater ) were significantly more abundant near rural homes, but nests of American Robins were not parasitized and their nest success did not differ with home density. Nests of Yellow Warblers were commonly parasitized by cowbirds, and their nest success was significantly lower near rural homes. Estimated intrinsic population growth ( � ) for American Robins suggested that low-elevation hotspots were population source areas for this species. Estimatedfor the Yellow Warbler suggested that the entire study area was a population sink, likely due to the effects of intense land use at lower elevations and cli- mate constraints at higher elevations. Removing the effect of land use from the simulations revealed that high- elevation hotspots were population sinks, whereas low-elevation hotspots were source areas. Our results are consis- tent with the possibility that bird-population source areas outside nature reserves can be converted to population sinks by intense human use, thereby reducing the viability of subpopulations within reserves. Factores Biofisicos, Uso de Suelo y Viabilidad de Especies en Reservas Naturales y sus Alrededores
TroX: a new method to learn about the genesis of aneuploidy from trisomic products of conception

Motivation: An estimated 10–30% of clinically recognized conceptions are aneuploid, leading to spontaneous miscarriages, in vitro fertilization failures and, when viable, severe developmental disabilities. With the ongoing reduction in the cost of genotyping and DNA sequencing, the use of high-density single nucleotide polymorphism (SNP) markers for clinical diagnosis of aneuploidy and biomedical research into its causes is becoming common practice. A reliable, flexible and computationally feasible method for inferring the sources of aneuploidy is thus crucial. Results: We propose a new method, TroX, for analyzing human trisomy data using high density SNP markers from a trisomic individual or product of conception and one parent. Using a hidden Markov model, we infer the stage of the meiotic error (I or II) and the individual in which non-disjunction event occurred, as well as the crossover locations on the trisomic chromosome. A novel and important feature of the method is its reliance on data from the proband and only one parent, reducing the experimental cost by a third and enabling a larger set of data to be used. We evaluate our method by applying it to simulated trio data as well as to genotype data for 282 trios that include a child trisomic for chromosome 21. The analyses show the method to be highly reliable even when data from only one parent are available. With the increasing availability of DNA samples from mother and fetus, application of approaches such as ours should yield unprecedented insights into the genetic risk factors for aneuploidy. Availability and implementation: An R package implementing TroX is available for download at http://przeworski.uchicago.edu/ Contact: ude.ogacihcu@ynamrek Supplementary information: Supplementary data are available at Bioinformatics online.
Early invasive versus ischaemia-guided strategies in the management of non-Q wave myocardial infarction patients with and without prior myocardial infarction. Results of Veterans Affairs Non-Q Wave Infarction Strategies In Hospital (VANQWISH) trial

Aims To compare the role of early invasive vs conservative management strategies in treating patients with non-Q wave myocardial infarction with or without a prior myocardial infarction. Background In patients recovering from non-Q wave myocardial infarction, the prognosis among patients with a first non-Q wave myocardial infarction is significantly better than in patients with a prior myocardial infarction, yet physicians often adopt an early invasive strategy to treat patients with a first non-Q wave myocardial infarction. Methods Non-Q wave myocardial infarction patients enrolled in the VANQWISH trial with a history of prior myocardial infarction were compared to those with a first non-Q wave myocardial infarction, for the trial primary end-point of death or myocardial infarction at 1 and 12 months, as well as for the initial randomized treatment strategy. Results Of the 920 non-Q wave myocardial infarction patients, 396 had a history of prior myocardial infarction and 524 did not. Patients with a history of prior myocardial infarction were older and had a higher incidence of multiple high-risk baseline characteristics than those with a first non-Q wave myocardial infarction. Compared to the group with a first myocardial infarction, the prior myocardial infarction group suffered more events at both 1 month (11% vs 6%, P =0·007) and at 12 months (29% vs 16%, P <0·001). This difference in outcome remained significant even after adjusting for confounding variables ( P <0·0001 at 12 months). Among the non-Q wave myocardial infarction patients with a prior myocardial infarction, the frequency of death or recurrent myocardial infarction was similar in both invasive and conservative groups during the first year of follow-up. Among the first non-Q wave myocardial infarction group, those assigned to the conservative strategy had significantly fewer events (3% vs 9%, P =0·009 at 1 month; 12% vs 20%, P =0·016 at 12 months) and mortality (1% vs 5%, P =0·012 at one month; 5% vs 11%, P =0·009 at 12 months) than those assigned to early invasive strategy. Conclusion A history of prior myocardial infarction identifies a moderately high-risk subset of non-Q wave myocardial infarction patients who display similar long-term outcomes regardless of the strategy assignment; however, patients with a first non-Q wave myocardial infarction may fare better with a conservative or ischaemia-guided approach during the first post infarction year.
Modularity in Development and Why It Matters to Evo-Devo1

The concept of modularity is fundamental to research in both evolutionary and developmental biology, though workers in each field use the idea in different ways. Although readily and intuitively recognized, modularity is difficult to define precisely. Most definitions of modularity are operational and implicit, particularly in developmental biology. Examination of several proposed definitions points to some general characteristics of developmental modules, for example their internal integration, and suggests the importance of devising a definition applicable at different levels of the biological hierarchy. Modules, like homologs, must be defined with respect to a specified level of the hierarchy, and a general definition should support both analyses of the evolving causal relationships between levels, and studies of the interconnections between modules of the same type. The designation of a developmental structure, process, or function as a “module” is a testable hypothesis; this hypothesis is confirmed in the case of the dorsal marginal zone of the amphibian gastrula, which acts as a morphogenetic module. Discussions of developmental modularity can provide a meeting place for developmental and evolutionary biologists by helping us articulate key questions at the intersection of the two fields, and design experiments to begin answering them.