cssi/SciSciGPT-SciSciNet huggingface dataset:
Apoptosis induced with different cycle-perturbing agents produces differential changes in the fluorescence lifetime of DNA-bound ethidium bromide.

Fluorescence lifetime analysis was used in combination with conventional flow cytometric analysis to monitor changes in residual chromatin in apoptotic HL-60 cell populations following treatment with camptothecin, cycloheximide, genistein, H7, and gamma radiation. Data presented show that all of these metabolic inhibitors, which act through different signaling cascades, produce apoptotic subpopulations with decreased but different lifetimes for DNA-bound ethidium bromide (EB). Additionally, treatment with certain agents reduced the fluorescence lifetime in the apoptotic cells prior to extensive endonuclease degradation of DNA and the appearance of the typical sub-G0/G1 peak in the DNA histogram. A lifetime value of 21.15 ± 0.12 ns was obtained for EB bound to nonapoptotic cells, while values for EB bound to the apoptotic subpopulations following treatment with the different agents were: camptothecin, 19.87 ± 0.08 ns; cycloheximide, 19.39 ± 0.02 ns; H7, 19.77 ± 0.03 ns; genistein, 20.04 ± 0.04 ns; and gamma radiation, 19.67 ± 0.03 ns. Traditional methods of analysis, including gel electrophoresis or morphology assessment, revealed no significant differences among apoptotic subpopulations induced by treatment with these agents. Our data suggest that the mode of action of the various agents induces structural changes in chromatin organization that differentially alter accessibility of DNA to endonuclease digestion. Subsequent fluorescence lifetime analysis appears sensitive to the resulting differences in the residual chromatin in apoptotic cells following DNA cleavage. Results presented indicate that lifetime analysis, used in conjunction with conventional flow cytometry, can be useful for early detection of apoptosis-induced chromatin changes and may also potentially provide new information on the effects of different apoptosis-inducing agents. Cytometry 31:208–216, 1998. © 1998 Wiley-Liss, Inc.
Neutron interactions and atomic recoil spectra

Abstract This paper presents a discussion of neutron interactions with materials that lead to activation, transmutation, and atomic displacements. The emphasis will be on current applications including neutron irradiation facilities, neutron dosimetry techniques, and computer codes for spectral adjustment and radiation damage calculations.
Comparison of the diffraction theory of image formation with the three-dimensional, first Born scattering approximation in lens systems

Abstract The Kirchoff diffraction theory of image formation is compared with the tree-dimensional, first Born scattering approximation for semitransparent objects imaged through a lens system. The comparison reveals the spatial frequency range over which the ‘equivalent two-dimensional, flat object’ represents the actual three-dimensional object in the imaging process.
New observation of a phase boundary in oxygen deficient YBa2Cu3O7−δ single crystals

Abstract We have measured the superconducting transition temperature Tcof oxygen deficient single crystals of YBa2Cu3Ox, where x = 7−δ in the range 6.5 T ∗ . We associate T ∗ with the onset of a transition from a vacancy ordered low temperature (ortho II and/or ortho III) phase to a high temperature ortho I phase. The nature of the vacancy ordering below T ∗ varies with x. We believe that, upon heating above T ∗ , a signigicant concentration of chain fragments develops in normally vacant chains of the ordered structure. When the crystals were quenched from temperatures above T ∗ , and subsequently permitted to anneal at 51°C, two relaxation processes were found. The two processes have relaxation times differing by about two orders of magnitude. The faster relaxation process is associated with changes in vacancy short-range disorder. The slower process is attributed to restoration of long-range chain vacancy order as misplaced fragments anneal out. T ∗ is determined for different oxygen concentrations and compared to theoretical phase diagram calculations. Electron diffraction measurements on well annealed single crystals with stoichiometries x = 6.50 and 6.65 show that different chain ordered phases (primarily ortho II and ortho III, respectively) exist at each of these compositions. Chain vacancy order is also observed at temperatures above T ∗ .
Effect of nighttime temperature on tomato plant defensive chemistry.

Given that the amplitude of diurnal temperature fluctuations has been decreasing, mainly via warmer night temperatures, we examined the effects of nighttime temperature on concentration of the catecholic phenolics chlorogenic acid and rutin in tomato plants. A two-factor design, with carbon dioxide (350 ppm and 700 ppm) and nighttime temperature (14, 15, 16, 17, and 18°C, with a 26°C daytime temperature) was used. Compared to the lower carbon dioxide level, for whole plants the concentration of phenolics was lower at the higher carbon dioxide level, but patterns for plant parts differed. Nighttime temperature did not affect concentration of phenolics for whole plants, but it did influence concentration of the phenolics for plant parts, although not in predictable ways. Furthermore, the pattern of concentration of chlorogenic acid was somewhat different from that of rutin. The amount of change in concentration of these allelochemicals is likely sufficient to have substantial effects on insect herbivores. We conclude that nighttime temperature affects concentration of allelochemicals in tomato plants in significant ways.
On measuring the effects of higher energy prices

Abstract The dramatic increases in world petroleum prices in the 1970s have been recognized as stimulating significant adverse economic consequences. Several simple partial equilibrium models have been constructed to analyse a portion of the expected consequences and some complex large-scale general equilibrium models have attempted the complete analysis. A simple and small general equilibrium model is developed and presented here that allows one to simply investigate and explain the effects of higher energy prices. The model is calibrated to the US experience over 1973–1979.
Clinical development of panobinostat in classical Hodgkin's lymphoma

Deacetylase (DAC) inhibitors are promising new anticancer drugs that have complex mechanisms of action, including induction of cell-cycle arrest and apoptosis, inhibition of angiogenesis and induction of a favorable anti-tumor immune response. Panobinostat, a potent inhibitor of DAC 1-11 enzymatic activity, has demonstrated a significant in vitro antiproliferative activity against classical Hodgkin's lymphoma (cHL) cell lines in addition to a promising clinical activity in early Phase I studies in patients with relapsed cHL. In a recently completed large Phase II study in patients with relapsed cHL, panobinostat reduced tumor measurements in 74% of patients, including 23% partial and 4% complete remissions. In this article, we review the status of panobinostat drug development and compare its activity to those of other DAC inhibitors in patients with relapsed cHL. Future investigations should focus on designing rational combination regimens and identifying predictive markers that will assist in selecting patients who are likely to benefit from this novel therapy.
Numerical evidence of stationary and breathing concentration patterns in the Oregonator with equal diffusivities

The set of three reaction-diffusion equations describing the time-space behavior of the intermediate chemical species in the Oregonator model of the Belousov-Zhabotinsky reaction is investigated in an open, gel-disk reactor in one and two spatial dimensions. Numerical simulations using equal values of the three diffusion coefficients indicate the presence of solutions corresponding to large-amplitude, apparently stable, stationary concentration patterns. The requirement of differential transport rates of chemical activator and inhibitor species for the development of stable patterns is apparently met in this system by differential exchange rates with the reservoir(s) rather than by differential diffusion rates within the gel-reactor. The characteristics of these patterns as well as their stability and bifurcation properties are investigated and suggest that their appearance is dependent upon the existence of bistability in the homogeneous reaction kinetics. The patterns have an intrinsic wavelength, and one of a particular wave-number destabilizes via a Hopf bifurcation as the length of the gel-reactor is varied, giving rise to oscillatory breather-solutions past the bifurcation but before decomposition into a spatially homogeneous state occurs. The relationship of these results to experimental systems, as well as an analogy to the behavior of biological membranes, is discussed.
Urban ecosystems: What would Tansley do?

The ecosystem concept was introduced in ecology originally to solve problems associated with theories of succession and ecological communities. It has evolved to become one of ecology’s fundamental ideas, and has proven to be applicable to a wide variety of research questions and applications. However, there is controversy about whether or how well the ecosystem concept is suited to urban habitats. By examining Arthur Tansley’s original presentation of the ecosystem concept, and exploring how the ecological context of the concept has changed, we indicate that the fundamental concept of the ecosystem is well suited to urban ecological studies. The concept can be clarified for urban use by including a social complex and a built complex to insure that human social institutions and actions, and the structures and infrastructure they build are explicitly included in the ecosystem concept. The ecosystem concept is thus seen as clearly robust to use in urban areas.
Three-Dimensional Natural Convection From Vertical Heated Plates With Adjoining Cool Surfaces

Natural convection in an enclosure with a uniform heat flux on two vertical surfaces and constant temperature at the adjoining walls has been investigated both experimentally and theoretically. The thermal boundary conditions and enclosure geometry render the buoyancy-induced flow and heat transfer inherently three dimensional. The experimental measurements include temperature distributions of the isoflux walls obtained using an infrared thermal imaging technique, while the three-dimensional equations governing conservation of mass, momentum, and energy were solved using a control volume-based finite difference scheme. Measurements and predictions are in good agreement and the model predictions reveal strongly three-dimensional flow in the enclosure, as well as high local heat transfer rates at the edges of the isoflux wall. Predicted average heat transfer rates were correlated over a range of the relevant dimensionless parameters.
An assessment of heterocoagulation theories

Abstract This article reviews different heterocoagulation theories and their principles and limitations. In view of existing discrepancies, an assessment is made by considering the fundamental aspects of double layer interactions.
Sarcomatoid renal cell carcinoma with massive osteosarcomatous differentiation: an unusual image in clinical urology.

A 46-year-old Hispanic woman presented with a 3-year history of a gradually enlarging right upper quadrant abdominal mass. The serum alkaline phosphatase was 2496 IU/L (normal 13 to 126 IU/L). Computed tomography of the chest, abdomen, and pelvis revealed an enormous, densely calcified mass arising from the kidney with no evidence of metastases (Fig. 1). A bone scan demonstrated increased tracer activity in the area of the mass with no evidence of skeletal metastases (Fig. 2). Radical nephrectomy revealed an almost entirely ossified mass measuring 20.5 cm in its greatest dimension. The histopathologic examination revealed a high-grade malignant neoplasm with extensively calcified osteoid that had features of an osteosarcoma. On electron microscopy, the malignant neoplastic cells showed the presence of desmosomes, indicating epithelial derivation (Fig.
Detritus decomposition and nutrient dynamics in a forested headwater stream

Abstract Field experiment and modeling studies have shown that microbial processes during leaf decomposition can modify detritus nutrients and inorganic nutrients in the system. In this study, we developed three models (Models I, II, and III) for leaf decomposition in a shaded headwater stream with little nutrient input, and we predicted the nutrient patterns in the stream. We used data from Hugh White Creek, NC, and synthesized several important ecological concepts from previous studies, i.e., ecological stoichiometry, microbial nutrient mining, and microbial–substrate interaction. In Model I, we calculated decomposition based on microbial metabolism rather than using first-order decay; in Model II, we further added an alternative microbial nutrient acquisition mechanism in which microorganisms (miners) mine detritus nutrients rather than using nutrients from stream water; and in Model III, we additionally broke detritus into three substrate groups (labile, intermediate, and recalcitrant material). Results showed that Model I fit the nutrient data the poorest; for the other two models, Model III performed better in fitting nitrate and Model II did slightly better in fitting ammonium; Models II and III predicted similar nutrient patterns, which were different from the patterns by Model I, suggesting that microbial mining may play an important role in decomposition.
Molecular emissions from laser–solid‐target interactions

When a high‐power Nd/glass laser pulse is incident on a polyethylene target, a bright plasma plume is created. Subsequently, a cloud of un‐ionized gas is formed which contains 10–100 times the amount of material in the plasma plume. This gas cloud is cold (expansion velocity ∼105 cm/sec) and dense (n≳1019). It is shown to contain diatomic molecules of carbon C2 by heating the core of the cloud with the pulse from a 1‐kJ TEA CO2 laser. Then, the C2 molecules in the cold outer regions of the cloud are seen in absorption on the light emitted by the hot core.
Use of complementary and alternative medicine by persons with arthritis: Results of the National Health Interview Survey

Objective To compare the complementary and alternative medicine (CAM) used by adults ages 45 years and older with and without arthritis, and to investigate the prevalence and predictors of CAM use by persons who report being told by a doctor they had arthritis. Methods Data from the 2002 National Health Interview Survey with a supplemental section on CAM use were analyzed. Data on overall use and use by 4 CAM modalities were calculated by arthritis status. CAM use for treatment of any health condition, including arthritis, was calculated and compared by arthritis status. Logistic regression was used to identify predictors of CAM use among persons with arthritis. Results Overall use of CAM and use of 3 of 4 major CAM categories were higher for persons who reported doctor-diagnosed arthritis compared with those without arthritis. Biologically based therapies were the most frequently reported modalities. Although persons with arthritis were more likely than those without arthritis to report using CAM for treatment, most of their CAM use was for conditions other than arthritis. Joint pain and poor functional status were the most common predictors of CAM modalities among persons with arthritis. Conclusion Health care providers of persons with arthritis should be aware that CAM use is common among their patients. A complete medication history is needed to obtain information on CAM use for all conditions.
Distributed object-oriented database programming using Java

The Java programming language allows programs developed to access data across the Inter-Net. One of the main applications of this technology is distributed databases. In this paper we investigate the use of Java as a language for manipulating object-oriented databases and also the Remote Method Invocation (RMI) package for distributing this data. We were able to allow distributed access to a database from multiple clients on a variety of different machines.
Acidic environment causes apoptosis by increasing caspase activity.

An exposure of HL-60 human promyelocytic leukaemia cells to acidic media with pH 6.2–6.6 caused an up-regulation of Bax protein expression within 2 h, which lasted for longer than 6 h. On the other hand, the apoptosis, as judged from PARP cleavage, DNA fragmentation and flow cytometric determination of cell population with sub-G1 DNA content, occurred after the cells were incubated in the acidic media for longer than 4 h. The PARP cleavage and DNA fragmentation in the cells exposed to an acidic environment could be effectively suppressed by inhibitors specific for ICE or CPP32, indicating that activation of these caspases is an essential step in acidic stress-induced apoptosis. It has been known that Bax is involved in the activation of caspases. Taken together, it appears that acidic stress first up-regulates Bax protein thereby activating caspases followed by PARP cleavage and DNA fragmentation. The observation that inhibition of either ICE or CPP32 could suppress acidic stress-induced apoptosis suggested that ICE activates pro-CPP32, which then cleaves PARP. Flow cytometric analysis indicated that acidic stress-induced apoptosis occurs mainly in G1 cells. The finding in the present study demonstrated that acidic intra-tumour environment may markedly perturb the tumour cell proliferation and tumour growth. © 1999 Cancer Research Campaign
Disulfide by Design 2.0: a web-based tool for disulfide engineering in proteins

Disulfide engineering is an important biotechnological tool that has advanced a wide range of research. The introduction of novel disulfide bonds into proteins has been used extensively to improve protein stability, modify functional characteristics, and to assist in the study of protein dynamics. Successful use of this technology is greatly enhanced by software that can predict pairs of residues that will likely form a disulfide bond if mutated to cysteines. We had previously developed and distributed software for this purpose: Disulfide by Design (DbD). The original DbD program has been widely used; however, it has a number of limitations including a Windows platform dependency. Here, we introduce Disulfide by Design 2.0 (DbD2), a web-based, platform-independent application that significantly extends functionality, visualization, and analysis capabilities beyond the original program. Among the enhancements to the software is the ability to analyze the B-factor of protein regions involved in predicted disulfide bonds. Importantly, this feature facilitates the identification of potential disulfides that are not only likely to form but are also expected to provide improved thermal stability to the protein. DbD2 provides platform-independent access and significantly extends the original functionality of DbD. A web server hosting DbD2 is provided at http://cptweb.cpt.wayne.edu/DbD2/ .
The phosphorylation of caveolin-2 on serines 23 and 36 modulates caveolin-1-dependent caveolae formation

Caveolin-1 and -2 are the two major coat proteins found in plasma membrane caveolae of most of cell types. Here, by using adenoviral transduction of either caveolin-1 or caveolin-2 or both isoforms into cells lacking both caveolins, we demonstrate that caveolin-2 positively regulates caveolin-1-dependent caveolae formation. More importantly, we show that caveolin-2 is phosphorylated in vivo at two serine residues and that the phosphorylation of caveolin-2 is necessary for its actions as a positive regulator of caveolin-1 during organelle biogenesis in prostate cancer cells. Mutation of the primary phosphorylation sites on caveolin-2, serine 23 and 36, reduces the number of plasmalemma-attached caveolae and increases the accumulation of noncoated vesicles, but does not affect trafficking of caveolin-2, interaction with caveolin-1 or its biophysical properties. Thus, the phosphorylation of caveolin-2 is a novel mechanism to regulate the dynamics of caveolae assembly.
A rigid surface boundary element for soil-structure interaction analysis in the direct time domain

Many soil-structure interaction problems involve studies of single or multiple rigid bodies of arbitrary shape and soil media. The commonly used boundary element methods implement the equations of the rigid body in a form that depends on the particulars of the geometry and requires partitioning and condensation of the associated algebraic system of equations. The present work employs the direct time domain B-Spline BEM for 3D elastodynamic analysis and presents an efficient implementation of rigid bodies of arbitrary shape in contact with, or embedded in, elastic media. The formulation of a rigid surface boundary element introduced herein is suitable for direct superposition in the BEM system of algebraic equations. Consequently, solutions are computed in a single analysis step, eliminating, thus, the need for partitioning of the system of equations. Computational efficiency is also achieved due to the extremely sparse form of the associated coefficient matrices. The proposed element can be used for the modeling of single or multiple rigid bodies of arbitrary shape within the framework of the BEM method. The efficiency and general nature of the proposed element is demonstrated through applications related to the dynamic analysis of rigid surface and embedded foundations and their interaction with embedded rigid bodies of arbitrary shape.
Downregulation of free ubiquitin: a novel mechanism of p53 stabilization and neuronal cell death.

Abstract Neuronal death through activation of the p53 stress response pathway has been implicated in the pathogenesis of neurodegenerative disorders. The mechanisms regulating p53 accumulation and function in neurons are poorly understood. Recent evidence has demonstrated that Mdm2 is a major inhibitor of p53 that binds to and targets p53 for ubiquitin-mediated degradation. Here we demonstrate increased expression and co-localization of p53 and Mdm2 in the nuclei of degenerating neurons following treatment with either the excitotoxin, kainic acid, or the topoisomerase I inhibitor, camptothecin. Co-immunoprecipitation studies showed that p53–Mdm2 complexes were present in neuronal lysates. Dual immunofluorescence microscopy demonstrated that these complexes accumulated in neurons with a striking decrease in free ubiquitin levels. Exogenous ubiquitin restored p53 degradation to extracts from injured neurons confirming that Mdm2 function was intact. Finally, antisense-mediated downregulation of ubiquitin in cultured hippocampal neurons resulted in p53 and Mdm2 accumulation as well as apoptotic death. These results point to a novel mechanism to stabilize p53 and promote neuronal cell death in the central nervous system.
Redox Reactions in Wheat Dough as Affected by Ascorbic Acid

Abstract Ascorbic acid (AA) is used as bread improver, as its addition to dough causes an increase in loaf volume and an improvement in crumb structure. To explain these effects we review the stereospecificity of the improver action and the properties of ascorbate oxidase and glutathione dehydrogenase and the occurrence of low molecular thiols in flour and their concentration changes during dough mixing in the presence and absence of AA. On the basis of the results the improver action of AA is explained by a reaction sequence leading to a rapid removal of endogenous GSH, which otherwise would cause dough weakening by sulphhydryl/disulphide interchange reactions with gluten proteins. To test this hypothesis the binding sites of endogenous GSH in gluten proteins have been determined by the addition of 35 S-labelled GSH as a tracer to flour before dough mixing. The distribution of radioactivity in the gliadin and glutenin fractions of gluten obtained from dough indicates that the major portion of GSH is bound to glutenins. The isolation and sequence analysis of radioactive cystine peptides from an enzymatic digest of glutenins demonstrates that GSH is almost exclusively linked to those cysteine residues of LMW subunits that have been proposed to form intermolecular disulphide bonds.
Degradation of labeled propionic and acetic acids.

Abstract A procedure for the stepwise degradation of the lower, straight-chain, saturated fatty acids has been developed which utilizes the Schmidt reaction for decarboxylation of the acid, followed by permanganate oxidation of the resulting amine. The adaptation of this method to the assay of isotopic concentrations of individual carbon positions of propionic and acetic acids on a semimicro scale is described. Radioactivity measurements on the degradation products of known C 14 -labeled compounds have shown a very low cross-contamination between individual carbon positions.
Bandwidth allocation strategies for transporting variable bit rate video traffic

Large-scale deployment and successful commercialization of digital video services over computer networks strongly depend on the cost effectiveness of these services. Network bandwidth is one of the major factors that impact the cost of a video service. We survey various approaches to reducing the bandwidth requirement for transporting compressed video traffic over high-speed networks.
An overview of concealed weapons detection for homeland security

There is an immediate requirement for law enforcement and homeland security to identify concealed weapons which may present a threat to official personnel and the general public. This involves suicide bomb vests, handguns, knife blades, and other threatening weapons. The weapons may be composed of a large range of materials such as metals, nonmetals, plastics and explosives. The Homeland Security Advanced Research Projects Agency (HSARPA) and the National Institute of Justice (NIJ) are presently funding programs collectively covering all relevant portions of the electromagnetic spectrum and ultrasound in order to detect these weapons through the various materials that may be used to conceal these weapons This paper outlines the various imaging techniques being investigated and present results where available
Ozone 17O quadrupole transitions in chloroform glass

Abstract 17O pure quadrupole transitions have been detected in ozone dissolved in a chloroform glass at 1.5°K with a field-cycling proton double resonance spectrometer. A broad resonance centered at 5.50 MHz is tentatively assigned to unresolved v 3 2 ↔ 1 2 and v 5 2 ↔ 3f 2 transitions, from terminal oxygen atoms. The assignment of another broad resonance centered at 11.30 MHz, presumably from the central oxygen, is uncertain.
Out of Bounds: Demanding Recognition for a Queer Identity

In this paper, the author utilizes a supervisory exchange as a springboard for a discussion of the issue of heteronormative privilege. She discusses the erasure of queer desire within a framework of normative heterosexuality and ties this to larger questions about recognition.
Fetal Expression of the Angiotensinogen Gene

To determine whether the angiotensinogen (Ao) gene is expressed in multiple organs of the fetal rat and the changes associated with maturation, fetal (15-20 days of gestation), newborn (1-10 days old), and adult (90 days old) rat tissues were subjected to Northern analysis and hybridization with a full length Ao complementary DNA (cDNA). Whereas Ao messenger RNA (mRNA) was undetectable in fetal livers, Ao sequences were readily detectable 1 h after birth and reached a peak at 24 h of birth. Levels remained elevated at 5 and 10 days after birth to decrease slightly at 90 days of postnatal life. Poly A+ enriched liver RNA was subjected to a similar analysis demonstrating that fetal liver Ao mRNA levels were 50-fold less than the corresponding adult levels. In contrast to the finding in the fetal liver, Ao mRNA was found in fetal brown fat, brains, and kidneys. We conclude that 1) Expression of the Ao gene is developmentally regulated in a tissue-specific manner; 2) Unlike the adult animal, the liver may not be the primary source of Ao in the fetus; 3) Alternate sources of Ao synthesis include fetal brown fat, brain, and kidneys.
Kinship care and sibling placement: Child behavior, family relationships, and school outcomes ☆

Abstract Using Child Protective Services (CPS) and Long Term Foster Care (LTFC) samples from the National Study of Child and Adolescent Well-being (NSCAW), this study examines 2488 observations of 1415 different children to investigate relationships among kinship foster care, sibling placement, and child welfare outcomes, including youth behavior, family and caregiver relationships, and school performance. Although a growing body of literature has addressed issues of kinship placement and sibling placement, no prior studies have examined outcomes of both types of placement, including possible interactions when placements involve kinship foster care of sibling groups. This article first provides an overview of research concerning outcomes of kinship foster care or joint placement of siblings in foster care. Following discussion of the study's samples and variables, the article presents both descriptive and regression analyses of outcomes. It concludes with a discussion of the substantive findings, their implications, and limitations.
The rationale for computer based treatment of language difficulties in nonspeaking autistic children.

The principles underlying a computer-based treatment method for language acquisition in nonspeaking autistic children are described. The main principle involves encouragement of exploratory learning with minimum adult interference.
VOICES: HEALTH + CARE IN THE UK

The British health care system has come under increasing scrutiny as people ask whether the billions of pounds spent each year are actually contributing to a healthier nation. Elizabeth Teisberg says the UK needs to drive improvement in value to help people enjoy hardier, longer and more productive lives — without raising costs.
Design-for-Testability for Synchronous Sequential Circuits that Maintains Functional Switching Activity

Design-for-testability (DFT) approaches that allow a synchronous sequential circuit to enter states that it cannot enter during functional operation improve the fault coverage achievable for the circuit. However, nonfunctional operation during test application may result in switching activity that is significantly higher than under functional operation. This may lead to unnecessary yield loss due to supply voltage droops that slow the circuit but will not occur during functional operation. To address this issue we describe a DFT approach and a test generation procedure that improve the fault coverage by slowing down the state transitions of certain state variables relative to others. Unlike approaches that are based on holding values of state variables stable for unlimited numbers of clock cycles, the proposed approach resumes functional operation every limited number of clock cycles. This is shown to result in maximum switching activity that is in most cases lower than that obtained under the application of a functional test sequence, and never needs to exceed it.
Walsh on Causes and Evolution

Denis Walsh has written a striking new defense in this journal of the statisticalist (i.e., noncausalist) position regarding the forces of evolution. I defend the causalist view against his new objections. I argue that the heart of the issue lies in the nature of nonadditive causation. Detailed consideration of that turns out to defuse Walsh’s ‘description‐dependence’ critique of causalism. Nevertheless, the critique does suggest a basis for reconciliation between the two competing views.
Stoichiometry of transjunctional voltage-gating polarity reversal by a negative charge substitution in the amino terminus of a connexin32 chimera.

Gap junctions are intercellular channels formed by the serial, head to head arrangement of two hemichannels. Each hemichannel is an oligomer of six protein subunits, which in vertebrates are encoded by the connexin gene family. All intercellular channels formed by connexins are sensitive to the relative difference in the membrane potential between coupled cells, the transjunctional voltage (Vj), and gate by the separate action of their component hemichannels (Harris, A.L., D.C. Spray, and M.V. Bennett. 1981. J. Gen. Physiol. 77:95–117). We reported previously that the polarity of Vj dependence is opposite for hemichannels formed by two closely related connexins, Cx32 and Cx26, when they are paired to form intercellular channels (Verselis, V.K., C.S. Ginter, and T.A. Bargiello. 1994. Nature. 368:348–351). The opposite gating polarity is due to a difference in the charge of the second amino acid. Negative charge substitutions of the neutral asparagine residue present in wild-type Cx32 (Cx32N2E or Cx32N2D) reverse the gating polarity of Cx32 hemichannels from closure at negative Vj to closure at positive Vj. In this paper, we further examine the mechanism of polarity reversal by determining the gating polarity of a chimeric connexin, in which the first extracellular loop (E1) of Cx32 is replaced with that of Cx43 (Cx43E1). The resulting chimera, Cx32*Cx43E1, forms conductive hemichannels when expressed in single Xenopus oocytes and intercellular channels in pairs of oocytes (Pfahnl, A., X.W. Zhou, R. Werner, and G. Dahl. 1997. Pflugers Arch. 433:733–779). We demonstrate that the polarity of Vj dependence of Cx32*Cx43E1 hemichannels in intercellular pairings is the same as that of wild-type Cx32 hemichannels and is reversed by the N2E substitution. In records of single intercellular channels, Vj dependence is characterized by gating transitions between fully open and subconductance levels. Comparable transitions are observed in Cx32*Cx43E1 conductive hemichannels at negative membrane potentials and the polarity of these transitions is reversed by the N2E substitution. We conclude that the mechanism of Vj dependence of intercellular channels is conserved in conductive hemichannels and term the process Vj gating. Heteromeric conductive hemichannels comprised of Cx32*Cx43E1 and Cx32N2E*Cx43E1 subunits display bipolar Vj gating, closing to substates at both positive and negative membrane potentials. The number of bipolar hemichannels observed in cells expressing mixtures of the two connexin subunits coincides with the number of hemichannels that are expected to contain a single oppositely charged subunit. We conclude that the movement of the voltage sensor in a single connexin subunit is sufficient to initiate Vj gating. We further suggest that Vj gating results from conformational changes in individual connexin subunits rather than by a concerted change in the conformation of all six subunits.
Ribozyme catalysis via orbital steering.

Orbital steering is invoked to explain how the three-dimensional structure of a small self-cleaving RNA, the hammerhead ribozyme, both prevents and enhances RNA autocatalysis. Within the conserved catalytic core of the ribozyme, the position of the 2' oxygen atom of the G8 ribose is observed to be aligned almost perfectly with the phosphorus atom and the 5' oxygen atom of the adjacent A9 phosphate group for self-cleavage via an in-line attack mechanism. Despite this apparent near-perfect atomic positioning, no cleavage takes place. The explanation proposed is that a network of hydrogen bonds in the ribozyme core orients or steers the orbitals containing the electron lone pairs of the attacking nucleophile (the 2' oxygen atom) away from the A9 phosphorus atom, eliminating overlap with the vacant phosphorus d-orbitals despite the near-perfect in-line positioning of the oxygen atom, thus preventing catalysis. Because of the near-perfect atomic positioning of the 2' oxygen atom relative to the phosphate group, orbital steering effects in this case are fortuitously uncoupled from conformational, distance and orientation effects, allowing an assessment of the catalytic power due purely to orbital steering. In contrast, a conformational change at the cleavage site is required to bring the 2' oxygen atom and the scissile phosphate group into atomic positions amenable to an in-line attack mechanism. In addition, the conformationally changed structure must then steer the lone-pair orbitals of the correctly positioned 2' oxygen atom toward the scissile phosphorus atom in order for cleavage to take place. We estimate that fulfillment of each of these two required changes may contribute separately an approximately 1000-fold rate enhancement, potentially accounting for a significant fraction of the catalytic power of this ribozyme. Orbital steering therefore appears to be a general phenomenon that may help to explain catalysis in both ribozymes and protein enzymes in a unified manner.
Alkaline phytase from Lilium longiflorum: purification and structural characterization.

Abstract Phytases catalyze the hydrolysis of phytic acid ( myo -inositol hexakisphosphate), the most abundant inositol phosphate in cells. Phytases are of great commercial importance because their use as food and animal feed supplement has been approved by many countries to alleviate environmental and nutritional problems. Although acid phytases have been extensively studied, information regarding alkaline phytases is limited. Alkaline phytases with unique catalytic properties have been identified in plants, however, there is no report on the purification or structural properties. In this paper, we describe the purification of alkaline phytase from plant tissue. The purification was challenging because of contamination from non-specific phosphatases and acid phytases and low endogenous concentration. The purification of alkaline phytase from pollen grains of Lilium longiflorum involved selective precipitation by heat and ammonium sulfate followed by anion exchange and chromatofocusing chromatography and, finally, gel electrophoresis. Alkaline phytase was purified ∼3000-fold with an overall recovery of 4.2%. The native molecular mass was estimated to be in the range of 118 ± 7 kDa by Ferguson plot analysis and M r of denatured protein in the range of 52–55 kDa by SDS–PAGE suggesting that the enzyme is a homodimer. Separation by 2-D gel and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometric analysis of separated proteins indicates the presence of multiple mass and charge isoforms with p I values between 7.3 and 8.3. To our knowledge, this is the first alkaline phytase to be purified from plant sources. The unique properties suggest that the enzyme has the potential to be useful as a feed and food supplement.
Sequential Perturbation Uncertainty Propagation in Thermal-Fluid Applications

A challenge in an undergraduate mechanical engineering curriculum is having students demonstrate “an ability to design and conduct experiments, as well as analyze and interpret data” as required for ABET accreditation. It is expected that students be able to identify and quantify sources of uncertainty, propagate uncertainties to intermediate and final results, interpret the relative importance of uncertainty sources, and develop experimental strategies to reduce the uncertainties in the final results. A spreadsheet application is presented that helps students learn these concepts and “see” what drives the uncertainty in the final results. The method known as sequential perturbation is used and shown to greatly reduce the tediousness of the calculations. As presented, the method significantly reduces the complexity of uncertainty analysis by eliminating the need to differentiate relationships between primary measurements and inferred measurements. Differentiation of complex relationships is often tedious and error-prone. The method is applied to three thermal-fluid application problems. Feedback from students is presented and is positive. The method summarized here should help students learn about the propagation of uncertainties and help demonstrate meeting ABET outcome “b”. The method can be extended beyond laboratory classes and is shown to be useful in design of experiments.Copyright © 2012 by ASME
Prevalence of the Neonatal Autopsy: A Report of the Study Group for Complications of Perinatal Care

Neonatal autopsy findings are valuable additions to the information base for current cases and future perinatal care, so the reported decline in the autopsy rate is disturbing. In order to estimate the prevalence of the neonatal autopsy among a large population of deaths, we surveyed participating institutions of the Study Group for Complications of Perinatal Care. Investigators from 37 neonatal intensive care units, located in 9 children's hospitals, 4 hospitals for women and infants, and 24 full-service pediatric and adult care hospitals, reported their neonatal death and autopsy rates for 1989. The overall neonatal autopsy rate was 51% among 1645 neonatal deaths. The rate was variable, ranging from 22 to 100%. We found the neonatal autopsy rate to be lower than previously reported and not apparently influenced by the type of center or by the type of medical staff at the centers. In order to assess and potentially reverse the current low rate, the influence of neonatal demographic and clinical factors, as well as physician-related factors, must be studied.
Structure and function of CarD, an essential mycobacterial transcription factor

CarD, an essential transcription regulator in Mycobacterium tuberculosis, directly interacts with the RNA polymerase (RNAP). We used a combination of in vivo and in vitro approaches to establish that CarD is a global regulator that stimulates the formation of RNAP-holoenzyme open promoter (RPo) complexes. We determined the X-ray crystal structure of Thermus thermophilus CarD, allowing us to generate a structural model of the CarD/RPo complex. On the basis of our structural and functional analyses, we propose that CarD functions by forming protein/protein and protein/DNA interactions that bridge the RNAP to the promoter DNA. CarD appears poised to interact with a DNA structure uniquely presented by the RPo: the splayed minor groove at the double-stranded/single-stranded DNA junction at the upstream edge of the transcription bubble. Thus, CarD uses an unusual mechanism for regulating transcription, sensing the DNA conformation where transcription bubble formation initiates.
Evolution from open surgical to endovascular treatment of ureteral-iliac artery fistula.

Purpose To review the indications and results of open surgical and endovascular treatment for ureteral-iliac artery fistula (UIAF). Methods We reviewed the clinical data of 20 consecutive patients treated for 21 UIAFs between 1996 and 2010. Since 2004, iliac artery stent grafts were the primary treatment except for complex fistulas with enteric contamination or abscess. Endpoints were early morbidity and mortality, patient survival, vessel or graft patency, freedom from vascular or stent graft/graft infection, and freedom from recurrent bleeding. Results There were 20 patients, 15 females, and five males, with mean age of 63 ±13 years. Predisposing factors for UIAF were prior tumor resection in 18 patients, radiation in 15, ureteral stents in 15, ileal conduits in four, and ileofemoral grafts in three. All patients presented with hematuria, which was massive in 10. Treatment included iliac stent grafts in 11 patients/12 fistulas (55%), with internal iliac artery (IAA) exclusion in nine, femoral crossover graft with IAA exclusion in five, direct arterial repair in three, and ureteral exclusion with percutaneous nephrostomy and no arterial repair in one. There were no early deaths. Five of eight patients treated by open surgical repair developed complications, which included enterocutaneous fistula in three and superficial wound infection in two. Four patients (36%) treated by iliac stent grafts had complications, including pneumonia, non-ST segment elevation myocardial infarction, buttock claudication, and early stent occlusion in one each. After a median follow-up of 26 months, no one had recurrent massive hematuria, but minor bleeding was reported in three. Patient survival at 5 years was 42% compared with 93% for the general population (P Conclusions UIAF is a rare complication associated with prior tumor resection, radiation, and indwelling ureteral stents. In select patients without enteric communication or abscess, iliac artery stent grafts are safe and effective treatment, and carry a low risk of recurrent massive hematuria or stent graft infection on early follow-up. Direct surgical repair carries a high risk of enterocutaneous fistula.
An Examination of the Effects of Offshore and Outsourced Development on the Delegation of Responsibilities to Software Components

Offshore and outsourced development are the latest facts of life of professional software building. The easily identifiable advantages of these trends – such as cost benefits, continuous delivery and support – have already been explored to considerable extent. But how does offshore and outsourced development affect the delegation of responsibilities to components of a software system? In this paper we investigate this question by applying the RESP-DIST technique on a set of real life case studies. Our RESP-DIST technique uses metrics and a linear programming based method to recommend the reorganization of components towards an expedient distribution of responsibilities. The case studies embody varying degrees of offshore and outsourced development. Results from the case studies lead to some interesting observations on whether and how offshore and outsourced development influences software design characteristics.
The Development of Infants' Spatial Categories

Early theories of how infants develop spatial concepts focused on the perceptual and cognitive abilities that contribute to this ability. More recent research, however, has centered on whether experience with spatial language might also play a role. The present article reviews how infants learn to form spatial categories, outlining the perceptual and cognitive abilities that drive this learning, and examines the role played by spatial language. I argue that infants' spatial concepts initially are the result of nonlinguistic perceptual and cognitive abilities, but that, as infants build a spatial lexicon, spatial language becomes an important tool in the spatial categories infants learn to form.
Ohno’s “Peril of Hemizygosity” Revisited: Gene Loss, Dosage Compensation, and Mutation

We explore the evolutionary origins of dosage compensation (DC) in sex chromosomes in the context of metabolic control theory. We consider first the cost of gene loss (hemizygosity) per se in reducing flux, and examine two relationships between flux and fitness (linear and Gaussian) to calculate a fitness cost of hemizygosity. Recognizing that new sex chromosomes are derived from autosomes, we also calculate the cost of unmasking deleterious mutations segregating on the nascent sex chromosomes as loci become hemizygous. The importance of deleterious mutations to the fitness cost of hemizygosity depends on their frequency, and on the relative costs of halving gene dose for wild-type alleles. We then consider the evolution of DC in response to gene loss, and include a cost of overexpression (i.e., DC such that expression exceeds the wild-type homozygote). Even with costs to excess flux, hypomorphic mutations can cause the optimal level of DC to be higher than 2-fold when the absolute cost of hemizygosity is small. Finally, we propose a three-step model of DC evolution: 1) once recombination ceases and the Y begins to deteriorate, genes from longer metabolic pathways should be lost first, as halving these genes does not drastically reduce flux or, thereby, fitness; 2) both the cost of hemizygosity and the presence of hypomorphic mutations will drive an increase in expression, that is, DC; 3) existing DC will now permit loss of genes in short pathways.