cssi/SciSciGPT-SciSciNet huggingface dataset:
Gene knockout and transgenic technologies in risk assessment: The next generation

Transgenic and knockout mice have been proposed as substitutes for one of the standard 2-yr rodent assays. The advantages of using genetically engineered mouse models is that fewer mice are needed, the time to develop disease is greatly reduced, and the mice are predisposed to developing cancer by virtue of gain or loss of functions. The models currently being used have yielded a large amount of data and have proved to be informative for risk assessment; however, they are still far from ideal. In fact, they inherently do not reflect the complexity of mutation and carcinogenesis in humans. Recent advances in technology and the creation of new knockout mice may produce more useful and more sensitive models. This review covers two recent advances in technology--inducible and regulatable gene expression and targeted genetic modifications in the genome--that will allow us to make better models. I also discuss new gene deletion and transgenic mouse models and their potential impact on risk-assessment assays. These models are presented in the context of four basic components or events that occur in the multistep process leading to cancer: maintenance of gene expression patterns, genome stability and DNA repair, cell-cell communication and signaling, and cell-cycle regulation. Finally, surrogate markers and utility in risk assessment are also discussed. This review is meant to stimulate further discussion in the field and to generate excitement about working toward the next generation of risk-assessment models.
Mnk earmarks eIF4E for cancer therapy

The PI3K/Akt/mTORC1 axis is perhaps the most frequently activated pathway in human cancers. Therefore, concerted efforts are being made to inhibit this pathway pharmacologically for cancer therapy. Although some success has been achieved, the multiple feedback loops that “litter” this pathway (ref. 1; Fig. 1), combined with the potential toxicity resulting from its inhibition, make the pharmacological targeting efforts very challenging. The ideal goal is to inhibit the functionality of the pathway in cancer cells without affecting normal cells and without eliciting feedback loops that could diminish the therapeutic efficacy. Back-to-back papers published in PNAS may provide this kind of therapeutic avenue (2, 3).
Femtosecond Dynamics of Electrons Photoinjected into Organic Semiconductors at Aromatic-Metal Interfaces

The layer dependent evolution of the unoccupied electronic structure and electron dynamics at the naphthalene/Ag(111) and the anthracene/Ag(111) interfaces have been investigated with femtosecond time and angle resolved two photon photoemission. With the exception of the peaks observed for the naphthalene monolayer, all excitations in the two photon photoemission spectra fit a hydrogenic progression, substantiating their assignment as image potential states. The monolayer excitations for naphthalene cannot be assigned as either image potential states or electron affinity (EA) levels, but rather as hybridized EA/image potential states. The binding energies and lifetimes of the image potential states for naphthalene and anthracene exhibit two significant differences that demonstrate the tremendous variation in the coupling between the image potential and the EA levels of naphthalene and those of anthracene. First, the binding energies at the naphthalene/Ag(111) interface exceed those of the anthracene/Ag(11...
Naming practice on an open platform for people with aphasia

Banga is a software system that uses the Android open source software platform for mobile phones to support word finding practice, a form of therapy for people with aphasia. By connecting to a Web site, Banga provides for remote monitoring and management of the therapy, making it easier for patients to participate in treatment, and for clinicians to deliver it.
Plasticizer-Free Polymer Containing a Covalently Immobilized Ca2+-Selective Ionophore for Potentiometric and Optical Sensors

A derivative of a known Ca2+-selective ionophore, ETH 129, was synthesized to contain a polymerizable acrylic moiety (AU-1) and covalently grafted into a methyl methacrylate-co-decyl methacrylate polymer matrix. The polymer containing AU-1 was prepared via a simple one-step homogeneous polymerization method. It exhibited mechanical properties suitable for the fabrication of plasticizer-free ion-selective membrane electrodes and bulk optode films by solvent-casting and spin-coating techniques, respectively. The segmented sandwich membrane technique was utilized to assess the binding constant of free and covalently bound ionophores to calcium and to study their diffusion coefficients in the membrane phase. Diffusion was greatly diminished for the bound ionophore. This was confirmed in ion-selective electrode membranes containing no calcium ions in the inner solution, which should normally show apparent super-Nernstian response slopes in dilute calcium solutions. The response slope was Nernstian down to subm...
Sterol Metabolism in the Rat: Effect of Alcohol on Sterol Metabolism in Two Strains of Rats

Sterol metabolism studies usinag a combination of iso-topic and chromatographic procedures were carried out in two strains of rats fed 5% ethanol (36% of calories) in the diet. Feeding ethanol to the Fisher rat over 17 days produced no significant changes in body weight. Cholesterol levels in various tissues were elevated in the ethanol-fed group: plasma cholesterol, +61%; liver cholesterol, +47%; and bile cholesterol, +57%. The alcohol-fed Fisher rat showed several changes in sterol metabolism over controls: fecal acidic steroid output, + 13%; fecal neutral sterol output, +51%; endogenous neutral sterol output, +107%; cholesterol turnover, + 54%; and cholesterol balance, +18%. Ethanol feeding to the Spraque Dawley rat showed similar differences between ethanol-fed vs. control rats. Cholesterol levels were significantly elevated in plasma (+35%) and in the liver (+81%). Sterol metabolism data showed the following differences (alcohol vs. control): fecal acidic steroid output, +9%; fecal neutral sterol output, +17%; endogenous neutral sterol output, +72%; cholesterol turnover, +33%; and cholesterol balance, +13%. The Fisher rat maintained almost constant weight throughout the experimental period and is a preferable strain for sterol balance studies using liquid diets. A major finding of these experiments was the increased concentration of cholesterol in liver, plasma, and bile in both strains of rats. The sterol balance measurements indicated that this tissue accumulation of cholesterol was due to enhanced cholesterol synthesis as well as inhibition of bile acid synthesis.
Prospects and Some Policy Problems of Agricultural Development in China

Chinese agriculture prior to the late 1970s is widely perceived to have had major shortcomings. The growth of output and of farm income was quite modest, productivity growth was negligible at best, and per capita consumption of food apparently suffered a slight long-term decline. Since 1978, by contrast, output growth has accelerated to a rate several times the long-term average, total factor productivity has jumped, and levels of food consumption have increased dramatically. The alltoo-frequent conclusion is that cooperative agriculture of the past was a failure, whereas the current arrangements-something akin to private household-based farming-provide the basis for sustained, reasonably rapid growth of agricultural output. The corollary of that view is that the current institutional arrangements are likely to persist in at least the medium-term future. The hypothesis I wish to advance here is that China's current institutional arrangements are not, in fact, likely to persist unaltered. While the shift toward household-based farming has alleviated some problems of the cooperative system, the current arrangements do not appear likely to provide the basis for sustained growth. In the mid-1980s China appears to be pursuing three major policy goals in agriculture-sustaining rapid growth, minimizing the state's commitment of resources for agriculture and rural development, and preserving some degree of collective ownership of the means of production, notably land. I argue below that these three goals cannot be achieved simultaneously, that one objective must be sacrificed. The choice is whether to accept a lower rate of growth of agricultural output, a higher level of state expenditures for agricultural development, or a further erosion in the degree of collective ownership and its resulting adverse effects on the distribution of rural income.
Transthoracic and transesophageal echocardiography for the indication of suspected infective endocarditis: vegetations, blood cultures and imaging.

Background The aim of this study was to investigate the ability of transthoracic echocardiography (TTE) to detect vegetations and the relationship between blood cultures and transesophageal echocardiography (TEE). Methods Five hundred eleven TTE and TEE pairs performed to evaluate endocarditis were retrospectively analyzed. Vegetation on TTE, prosthetic valve, change in regurgitation, and blood cultures were correlated with vegetation on TEE. Results TTE detected 45% of vegetations seen on TEE. There was no difference for prosthetic valves. Prosthetic valves (odds ratio, 1.7; P = .03) and increased regurgitation (odds ratio, 1.7; P = .01) were associated with vegetations on TEE; staphylococcal bacteremia and fungemia were not. Negative blood cultures were associated with negative results on TEE ( P Conclusion This study demonstrates a limited capacity of TTE to detect vegetations. TEE may be an appropriate initial study to evaluate prosthetic valves. TEE for culture-negative endocarditis deserves further study.
Influence of coating formulation variables and processing on the adhesion of melamine-crosslinked polyester primer to urethane-crosslinked epoxy electrocoat

The role of spray-primer formulation chemistry towards robustness of adhesion to an epoxy-based electrocoat was examined for a range of coatings representative of those used in automotive OEM applications. For coatings exhibiting degraded adhesion performance, high-resolution X-ray photoelectron spectroscopy (XPS) identified the presence of a surface-active polyether-based anti-cratering agent (ACA) formulated into the epoxy-based electrocoat at the primer/electrocoat interface. The adhesion performance of the better-performing systems was found to be related to the spray-primer’s ability to accommodate the ACA by either absorbing or displacing it from the electrocoat surface, thus diluting it to concentrations no longer adversely affecting adhesion.
The stability of interacting populations

Abstract A general Volterra model for describing the dynamics of interacting populations is proven to be inherently stable. Conditions are given under which, for any particular application of the model, each species in the community will either oscillate about its unique equilibrium value continuously in a limit cycle or approach it asymptotically. The asymptotic approach to the steady state is proven to be exponential eventually. An estimate of the decay constant indicates faster convergence to the steady state the larger the size of the equilibrium populations, the intra-species interaction, and the ‘ nutritional value ’ of the inter-species interaction.
The Evaluation of a Distributed Online Simulation during a Battalion Staff Exercise

A distributed simulation being developed by the U.S. Army using online gaming technology was evaluated during a Battalion staff exercise. The staff worked through a pre-deployment Stability and Support Operation (SASO) exercise to a hypothetical Middle-Eastern country, in which they acquired information about the local situation relevant to their assigned mission, then developed deployment and contingency plans for that mission. These plans were then evaluated by the Battalion Commander, and the staff was evaluated on their performance. Questionnaire information was collected from the staff about the effectiveness of the simulation, and interviews with the command staff and the commander provided opinion-based evidence of the value of the simulation system and simulated exercises of this kind. The results indicate considerable potential for systems of this nature to expand training and evaluation opportunities as well as meet new asymmetric training needs while optimizing Soldiers' training time.
Partnership for the Advancement of Information Literacy in a Nursing Program.

Nursing educators know that healthcare stakeholders expect nursing graduates to be able to manage information. Consequently, many nursing education programs are exploring ways of integrating information literacy across the curriculum not only to bolster evidence-based practice, but also to enhance professional development and encourage lifelong learning. By adding collaborative efforts between librarians and nursing educators, nursing students will be better prepared to meet workforce expectations, complete high stakes writing assignments, and will become active decision makers. This study describes a collaborative effort between nursing and library faculty in the quest to integrate information literacy in an Associate Degree nursing program.
Motion-based shape illustration

Motion provides strong visual cues for the perception of shape and depth, as demonstrated by cognitive scientists and visual artists. We present a novel visualization technique that uses particle systems to add supplemental motion cues. Based on a set of rules following perceptual and physical principles, particles flowing over the surface of an object not only bring out, but also attract attention to essential shape information of the object that might not be readily visible with conventional rendering. Replacing still images with animations in this fashion, we show with both surface and volumetric models that the resulting visualizations effectively enhance the perception of three-dimensional shape and structure.
Site-directed mutagenesis of the cysteine residues in the Neurospora crassa plasma membrane H(+)-ATPase.

Abstract A high-yield yeast expression system for site-directed mutagenesis of the Neurospora crassa plasma membrane H-ATPase has recently been reported (Mahanty, S. K., Rao, U. S., Nicholas, R. A., and Scarborough, G. A.(1994) J. Biol. Chem. 269, 17705-17712). Using this system, each of the eight cysteine residues in the ATPase was changed to a serine or an alanine residue, producing strains C148S and C148A, C376S and C376A, C409S and C409A, C472S and C472A, C532S and C532A, C545S and C545A, C840S and C840A, and C869S and C869A, respectively. With the exception of C376S and C532S, all of the mutant ATPases are able to support the growth of yeast cells to different extents, indicating that they are functional. The C376S and C532S enzymes appear to be non-functional. After solubilization of the functional mutant ATPase molecules from isolated membranes with lysolecithin, all behaved similar to the native enzyme when subjected to glycerol density gradient centrifugation, indicating that they fold in a natural manner. The kinetic properties of these mutant enzymes were also similar to the native ATPase with the exception of C409A, which has a substantially higher K. These results clearly indicate that none of the eight cysteine residues in the H-ATPase molecule are essential for ATPase activity, but that Cys, Cys, and Cys may be in or near important sites. They also demonstrate that the previously described disulfide bridge between Cys and Cys or Cys plays no obvious role in the structure or function of this membrane transport enzyme.
ERG and FLI1 protein expression in epithelioid sarcoma

Epithelioid sarcoma is a rare, aggressive keratin-positive sarcoma that co-expresses CD34 in 50% of cases and may mimic an angiosarcoma. Recently, we have observed one case of epithelioid sarcoma that labeled for ERG, an ETS family regulatory transcription factor, which is considered to be a reliable marker for vascular differentiation. We investigated the prevalence of nuclear expression of ERG and FLI1, a homologous transcription factor, in these tumors. A formalin-fixed paraffin-embedded tissue microarray of 37 epithelioid sarcomas was examined. Immunohistochemistry was performed using anti-ERG monoclonal antibody to the N-terminus, anti-ERG monoclonal antibody to the C-terminus and anti-FLI1 monoclonal antibody. Comparison was made with CD34, CD31, and D2-40 labeling. The extent of immunoreactivity was graded according to the percentage of positive tumor cell nuclei (0: no staining; 1+: <5%; 2+: 5-25%; 3+: 26-50%; 4+: 51-75%; and 5+: 76-100%), and the intensity of staining was graded as weak, moderate, or strong. Nuclear staining for the N-terminus of ERG was seen in 19 out of 28 cases: 10 with diffuse(4 to 5+) strong/moderate labeling; 1 with 2+ moderate labeling and 8 with weak labeling (1 to 4+, 2 each). Focal staining for the C-terminus of ERG was seen in only 1 out of 29 cases (2+ moderate). FLI1 labeling was seen in nearly all (28 out of 30) cases: 16 with diffuse (5+) predominantly moderate labeling, and 8 cases with diffuse(5+) weak labeling. The remainder had variable moderate (1 to 3+) or weak (1 to 4+) FLI1 staining. CD34 was positive in 22 out of 30 cases and D2-40 was found to be positive in 22 out of 31 cases. All cases were negative for CD31 (0 out of 30). Epithelioid sarcoma can label with antibodies to the N-terminus of ERG, FLI1, and D2-40, which may cause diagnostic confusion for a vascular tumor. A panel of other antibodies including SMARCB1 and CD31 should be used in evaluating these tumors. ERG antibody selection is also critical, as those directed against the C-terminus are less likely to label epithelioid sarcoma.
Lawyers With Disabilities: L’Handicape C’est Nous

For having helped to make disability a twentieth-century civil rights issue in the United States, our profession deserves much credit. Lawyers have written, codified, and enforced several progressive initiatives. Inspired by the struggle for racial justice through law that culminated in Brown v. Board of Education, the disability rights movement was itself a civil rights inspiration even before the Brown decision, earning important early legislative advances for rehabilitation, vocational training, and integration of disabled persons in public life. The first national organization to focus on disability as such rather than one particular condition, the American Federation of the Physically Handicapped, took an early interest in fostering legal change and lobbied for employment-discrimination laws and new statutes to advance the interests of disabled Americans. The Rehabilitation Act of 19733 made federal law out of the radical yet sensible idea that societies construct disability at least as much as they reflect it and that prejudices and stereotypes, which are as potent as purely medical or anatomical facts, impede persons with disabilities.
Biochemical and pathological studies of myelin in hexachlorophene intoxication

Summary Adult female rats were fed a diet containing 500 ppm hexachlorophene (HCP). Morphological study of brains from these animals showed vacuolation of the myelin sheaths due to separation of myelin lamellae at the minor dense line. However, myelin could be isolated from the brains of these animals in normal yield. The myelin isolated from HCP-fed animals had normal lipid and protein compositions as shown by analyses of the individual lipids and by disc gel electrophoresis of the proteins. Assay of the myelin-specific enzyme, 2′,3′-cyclic nucleotide-3′-phosphohydrolase, showed normal specific activity in myelin obtained from HCP-fed rats. Brains of HCP-fed rats showed an increase in wet weight and a decrease in dry weight, with the chloroform-methanol insoluble fraction showing the greatest weight loss. During isolation of myelin from HCP-fed rats material was found floating over 0.32 M sucrose. This ‘floating fraction’ contained a higher ratio of lipid to protein but the same relative proportions of the individual lipids as are found in myelin. The yield of ‘floating fraction’ from each HCP-fed rat was less than 10% of the yield of myelin. Disc gel electrophoresis demonstrated the presence of the usual myelin proteins in this fraction, but with a slight increase in the relative amount of the low molecular weight basic protein. The data were compared to reports on the biochemistry of triethyltin poisoning, and it was concluded that vacuolation of myelin in HCP poisoning is probably due to increased permeability of myelin lamellae to water and electrolytes.
Simulation of a high Reynolds number reactive transverse jet and the formation of a triple flame

Abstract This paper briefly describes a hybrid Eulerian–Lagrangian approach for the numerical simulation of turbulent combustion and its application to the study of transverse reactive jets. Because of their interesting mixing properties, transverse jets are important to a variety of industrial applications such as film cooling, primary or dilution jets in gas turbines, and flame stabilization in high speed combustion. To capture the jet complex structure and the associated reaction dynamics, we developed a fast, multiscale and parallel 3D code using a Lagrangian particle method to solve the vorticity transport equation and an Eulerian adaptive grid-based method to solve the reactive transport equations. Flame anchoring computations were done for a pure methane jet in a crossflow of air at a Reynolds number Re = 1000 and at a velocity ratio of 5 between the jet and the crossflow velocity. The results show that the reactive jet structure strongly resembles that of the non-reactive case, although the reactive jet is slower to bend into the cross flow and it is wider in the spanwise direction. The flame is anchored downstream of the nozzle in a relatively low velocity region and shows a triple flame structure. This triple flame seats in a region of relatively low scalar dissipation rate. We describe the three dimensional topology of the triple flame, as well as the impact of the jet counter-rotating vortex pair (CVP) on the flame front.
SU-E-T-497: Semi-Automated in Vivo Radiochromic Film Dosimetry Using a Novel Image Processing Algorithm

Purpose: To validate an automated image processing algorithm designed to detect the center of radiochromic film used for in vivo film dosimetry against the current gold standard of manual selection. Methods: An image processing algorithm was developed to automatically select the region of interest (ROI) in *.tiff images that contain multiple pieces of radiochromic film (0.5x1.3cm{sup 2}). After a user has linked a calibration file to the processing algorithm and selected a *.tiff file for processing, an ROI is automatically detected for all films by a combination of thresholding and erosion, which removes edges and any additional markings for orientation. Calibration is applied to the mean pixel values from the ROIs and a *.tiff image is output displaying the original image with an overlay of the ROIs and the measured doses. Validation of the algorithm was determined by comparing in vivo dose determined using the current gold standard (manually drawn ROIs) versus automated ROIs for n=420 scanned films. Bland-Altman analysis, paired t-test, and linear regression were performed to demonstrate agreement between the processes. Results: The measured doses ranged from 0.2-886.6cGy. Bland-Altman analysis of the two techniques (automatic minus manual) revealed a bias of -0.28cGy and a 95% confidence interval ofmore » (5.5cGy,-6.1cGy). These values demonstrate excellent agreement between the two techniques. Paired t-test results showed no statistical differences between the two techniques, p=0.98. Linear regression with a forced zero intercept demonstrated that Automatic=0.997*Manual, with a Pearson correlation coefficient of 0.999. The minimal differences between the two techniques may be explained by the fact that the hand drawn ROIs were not identical to the automatically selected ones. The average processing time was 6.7seconds in Matlab on an IntelCore2Duo processor. Conclusion: An automated image processing algorithm has been developed and validated, which will help minimize user interaction and processing time of radiochromic film used for in vivo dosimetry.« less
Detection of Tumor-derived DNA in Cerebrospinal Fluid

The sensitivity of PCR-based methods for the detection of DNA offers opportunities for tumor diagnosis from the small amounts of tumor-derived DNA released into body fluids. We report the detection of tumor DNA in the cerebrospinal fluid (CSF) of two patients with intracranial neoplasms. One patient had a metastatic breast carcinoma which contained amplified HER-2/neu genes, and amplified HER-2/neu gene sequences were present in her CSF. The other patient had a glioblastoma which contained amplified epidermal growth factor receptor (EGFR) genes, and amplified EGFR gene sequences were present in her CSF. This report demonstrates that CSF sometimes contains tumor-derived DNA and suggests that PCR examination of CSF DNA may be diagnostically useful.
American Indian intermarriage

Abstract An analysis of intermarriage patterns with data from the Public Use Microdata Sample of the 1980 Census shows that there is considerably more intermarriage between Indians and whites than between blacks and whites. Indians who live in traditional Indian areas are more likely to be endogamous than those who live in areas where Indians have not traditionally lived, though Indians in traditional Indian areas are also more likely to be married to whites than are Indians in nontraditional Indian areas (after adjustments are made to take into account the number of men and women in the different racial groups). The results also indicate that endogamous American Indians are poorer and less educated than any other type of couple, including endogamous black Americans.
Co-stimulated/Tc2 cells abrogate murine marrow graft rejection.

Abstract CD3/CD28 co-stimulation activates T-cell cytokine and cytolytic effector function and therefore represents an approach to modulate donor T cells before allogeneic bone marrow transplantation (BMT). We hypothesized that co-stimulation of donor T cells under T2 conditions would generate CD4+ T-helper type 2 (Th2) and CD8+ Tc2 cells capable of abrogating marrow graft rejection with reduced graft-versus-host disease (GVHD). Relative to control co-stimulated Th1/Tc1 (T1) cells, co-stimulated T2 cells secreted reduced interleukin (IL)-2 and interferon-γ and increased IL-4 and IL-10, expressed reduced fas ligand, and had similar total cytolytic capacity. In an F1-into-parent sublethal irradiation model, T2 cells potently abrogated rejection; this veto effect was partially attenuated if T2 cell infusion was delayed for 24 hours after BMT. Cell-tracking studies determined that T2 cells were quantitatively reduced after BMT when administered to hosts capable of mounting a host-versus-graft rejection response; both donor and host cytotoxic T lymphocytes may therefore have been deleted during Th2/Tc2 cell facilitation of engraftment. Donor T2 cells also abrogated rejection in an F1-into-parent model that used lethal host irradiation and subsequent host T-cell addback. Further experiments in a P1-into-P2 transplantation model demonstrated that donor T2 cells abrogated rejection with reduced GVHD in a transplant setting involving full major histocompatibility complex disparity in both the host-versus-graft and graft-versus-host directions. The capacity of T2 cells to abrogate rejection with reduced GVHD was a function of both the number of T2 cells infused and the number of T cells present after host preparation. Co-stimulation under T2 polarizing conditions therefore rapidly generates donor Th2/Tc2 cells that potently abrogate murine marrow rejection with reduced GVHD.
Dissociative alterations in body image among individuals reporting out-of-body experiences : A conceptual replication

A conceptual replication of the link between self-reported dissociative alterations in body-image under experimental conditions and the reporting of prior out-of-body experiences in a recent data set was undertaken. Also examined was whether this relationship would hold for experiences reported during the experimental context and whether it is independent of self-reported New Age belief. Data from mostly undergraduates (N= 40; M age = 33.5, SD = 12.5; 27 women) in a mirror-gazing study were retrospectively analyzed. The 9 individuals who reported prior out-of-body experiences, relative to those 31 who did not, exhibited significantly greater self-reported dissociative alterations in body-image during the mirror-gazing task, even when the influence of scores on New Age belief was controlled for statistically. The same differential relationship was not found between 6 individuals who did and 34 who did not report out-of-body experiences during the task.
A survey of current research studies on drug education programs in America.

This article surveys recent research findings on drug education programs in America. Findings have been somewhat contradictory but a pattern of encouraging results seem to favor prevention programs that focus on resistance training. Research results were complimentary of D.A.R.E. (Drug Abuse Resistance Education) and S.A.P. (Student Assistance Program) which emphasizes intervention strategies. Experts noted that drug education programs require interagency collaboration among schools, communities, and families. Authorities appealed for a higher funding priority toward evaluating the effectiveness of drug education programs. The article also provides information about what parents, schools, students, and communities can do concerning drug prevention efforts.
A HYBRID AUTOMATA APPROACH FOR ROBOTIC PERCEPTIVE CONTROL AND PLANNING

Abstract This paper presents a hybrid automata approach for modeling and analyzing the robotic motion planning and control. Robotic systems acquire data from perceptive sensors and respond to the perceptions through decision and control process. The hybrid perceptive framework is built based on continuous and discrete perceptive references. The robot can plan and modifying the original path through switching the continuous controller at discrete level. The hybrid system is stable in switching. The evolution of the hybrid references can be guaranteed during the unexpected events that can block the continuous or discrete references.
Effect of inflammation on the binding of colloidal particles to the surfaces of polymorphonuclear neutrophilic leukocytes

Abstract The surface binding of Thorotrast particles by polymorphonuclear neutrophilic leukocytes (PMNs) in the blood of guinea pigs has been studied by a method of quantitative cytochemistry. The average number of colloidal particles per micron length of surface membrane, i.e., particle density, has been evaluated on PMNs from normal animals and from animals 24 hours after the production of acute inflammation or cell-mediated immunity. There is a significant decrease in the mean particle density of PMNs in animals with both types of inflammation, thereby indicating a reduction in acidic ionogenic groups on the surfaces of PMNs. The possible role of surface alterations in the margination and emigration of leukocytes is discussed.
Assumptional Analysis: A Methodology for Strategic Problem Solving

This paper deals with the critical role that assumptions play in strategic planning and strategic problem forming. It attempts to formulate a methodology or systematic procedure for 1 uncovering surfacing, 2 analyzing the effect, and 3 challenging key policy assumptions. The paper shows how the dialectical approach to strategic planning first suggested by Churchman Churchman, C. W. 1971. The design of inquiring systems. Basic Books, New York; Churchman, C. W. 1968. The systems approach. Delacorte, New York. and Mason Mason, R. O. 1969. A dialectical approach to strategic planning. Management Sci.15 B-403--B-414. can put on a more systematic and operational basis such that it can serve as a useful methodology for addressing ill-structured, i.e., difficult-to-define, problems.
Hepatocyte Nuclear Factor-3 Homologue 1 (HFH-1) Represses Transcription of Smooth Muscle-specific Genes

Results show that smooth muscle-specific promoters represent novel downstream targets of the winged helix factor hepatocyte nuclear factor-3 homologue 1 (HFH-1). HFH-1 strongly represses telokin promoter activity when overexpressed in A10 vascular smooth muscle cells. HFH-1 was also found to repress transcription of several other smooth muscle-specific promoters, including the SM22α promoter. HFH-1 inhibits telokin promoter activity, by binding to a forkhead consensus site located within an AT-rich region of the telokin promoter. The DNA-binding domain alone was sufficient to mediate inhibition, suggesting that binding of HFH-1 blocks the binding of other positive-acting factors. HFH-1 does not disrupt serum response factor binding to an adjacent CArG box within the telokin promoter, implying that HFH-1 must compete with other unidentified trans-activators to mediate repression. The localization of HFH-1 mRNA to the epithelial cell layer of mouse bladder and stomach implicates HFH-1 in repressing telokin expression in epithelial cells. This suggests that cell-specific expression of telokin is likely mediated by both positive-acting factors in smooth muscle cells and negative-acting factors in nonmuscle cell types. We propose a model in which the smooth muscle specificity of the telokin promoter is regulated by interactions between positive- and negative-acting members of the hepatocyte nuclear factor-3/forkhead family of transcription factors.
Mammalogy in an Epidemiological Study of Jungle Yellow Fever in Brazil

Prior to 1932 yellow fever had been considered as strictly an urban disease, carried by the domestic mosquito, Aedes aegypti, in the classic cycle of manmosquito-man. In 1932, however, the Brazilian Yellow Fever Service, an organization maintained by the Brazilian Ministry of Education and Health with the cooperation of the International Health Division of The Rockefeller Foundation, discovered the disease in a rural area in the absence of Aedes aegypti (Soper, et al., 1933). This site, now historic from the standpoint of yellow fever, was the Valle de Chanaan, in the State of Espirito Santo, on the east coast of Brazil just north of Rio de Janeiro. The discovery marked a departure from the then current epidemiological beliefs regarding the disease, by calling for serious consideration of a different insect vector and a different vertebrate host (a jungle inhabitant) and also raised the question of possible control once the wild species in the newly discovered cycle were found. In late 1935, I joined the staff of the Yellow Fever Service and participated in the field investigations, involving clinical, laboratory, entomological, and vertebrate zoological aspects, which were begun as a joint operation at a field laboratory at Anapolis in the State of Goyaz. Studies were continued there throughout 1936 and 1937; another field laboratory was set up in the southern Matto Grosso in 1937; and in 1938 Fordlandia on the Rio Tapajoz near the Amazon, and the vicinity of Rio de Janeiro were the scenes of continued intensive field work. The solution of the problem of explaining all the epidemiology of jungle yellow fever is difficult, and is not yet complete; but it seems probable now (1941) that the disease is perpetuated by a cycle involving several species of wild mosquitoes and various mammals, especially monkeys and opossums. Control of these forms is not feasible, and an easily administered and effective vaccine has been developed as a solution to the problem of public health protection. The demand on the zoologist in the beginning was for the collection of specimens of blood serum for an immunity (mouse-protection) test from as many vertebrates as possible, particularly primates. For it had been shown by laboratory and field investigations, on monkeys and man, that recovery from yellow fever infection conferred a specific and lasting immunity in these species. Therefore, it was concluded that any species of wild animal whose blood sera showed a high percentage of immunes, could be seriously suspected of complicity in the natural jungle cycle of the disease. This was an indirect method to be sure, but the only direct way to pin guilt on a species of vertebrate would be to isolate the virus from the circulating blood of a wild-taken individual. This would not be as easy, however, as it sounds, because (1) no susceptible animals are known to harbor the virus more than a week or so (generally 3-4 days) after infectionthat is, there is no persistent infection, and (2) it would be necessary to guess several weeks ahead where yellow fever would occur in the human population 144
Control by calcium of the contractility of Labyrinthula slimeways and of the translocation of Labyrinthula cells

Colonies of Labyrinthula, a colonial marine protist, expand by protrusive movements of the specialized slimeways. The movements recorded in time-lapse films are of two types – filopodial and lamellipodial – and occur at rates equivalent to those of cell translocation. Evidence is presented that Ca2+ regulates the contraction of the actomyosin system of filaments present in the slimeways of Labyrinthula. In glycerinated models or in colonies exposed to ionophore A23187 contraction is evidenced by the occurrence of periodic contractions of the slimeways, giving them the appearance of strings of beads. Glycerinated slimeways contract on the addition of Ca2+ and ATP while slimeways provided with ionophore A23187 contract on addition of Ca2+ alone. The concentration required is 1.1 × 10−7 M Ca2+ while concentrations of 6.2 × 10−8 or lower were ineffective. Rates of contraction were measured in time-lapse films which provide evidence that contractions and beading occur everywhere in the slimeway system. When beading occurs, the 6-nm filaments transform from an array of parallel single filaments into an interwoven meshwork. We have identified by pyroantimonate-OsO4 fixation, as possible Ca2+ reservoirs, deposits of Ca2+ in bothrosomes – structures through which cell secretions pass into the slimeways. The electron-dense deposits are located at the base of the bothrosome and disappear after incubation with EGTA. We propose that the translocation of cells as well as the movements of slimeways may be regulated by the cells through the local measured liberation of Ca2+ from the bothrosome where it is sequestered.
Subunit exchange of lens α‐crystallin: a fluorescence energy transfer study with the fluorescent labeled αA‐crystallin mutant W9F as a probe

Abstract A Trp-free αA-crystallin mutant (W9F) was prepared by site-directed mutation. This mutant appears to be identical to the wild-type in terms of conformation (secondary and tertiary structures). W9F was labeled with a sulfhydryl-specific fluorescent probe, 2-(4′-maleimidylanilino) naphthalene-6-sulfonate (MIANS), and used in a subunit exchange between αA- and αA-crystallins as well as between αA- and αB-crystallins, studied by measurement of fluorescence resonance energy transfer. Energy transfer was observed between Trp (donor, with emission maximum at 336 nm) of wild-type αA- or αB-crystallin and MIANS (acceptor, with absorption maximum at 313 nm) of labeled W9F when subunit exchange occurred. Time-dependent decrease of Trp and increase of MIANS fluorescence were recorded. The exchange was faster at 37°C than at 25°C. The energy transfer efficiency was greater between homogeneous subunits (αA-αA) than between heterogeneous subunits (αA-αB). A previous exchange study with isoelectric focusing indicated a complete but slow exchange between αA and αB subunits. The present study showed that the exchange was a fast process, and the different energy transfer efficiencies between αA-αA and αA-αB indicated that αA- and αB-crystallins were not necessarily structurally equivalent.
Synthesis and assembly of adenovirus type 2 polypeptides. II. Reversible inhibition of hexon assembly at 42

Abstract Hexon polypeptides (monomers) synthesized at 42° do not assemble into capsomeres (trimers) until temperature stepdown to 37°. Structural studies of monomer and trimer show them to be identical in molecular weight and tryptic peptide patterns. Cyanide and mercaptoethanol, both of which can interact with sulfhydryl groups, inhibit hexon assembly. Therefore, the oxidation state of each sulfhydryl group of cysteine was examined, but was found to be the same for free polypeptides and capsomeres. These observations suggest that factors other than the primary structure of the polypeptides are important for in vivo assembly.
Abnormal concentrations of esterified carnitine in bile: A feature of pediatric acute liver failure with poor prognosis

The etiology of acute liver failure in children is unknown in a large number of cases. Defects in fatty acid oxidation have been shown to lead to severe liver injury. This retrospective analysis examined the bile acylcarnitine profiles of 27 children with acute liver failure who underwent liver transplantation or died. Results were compared with 758 postmortem samples from individuals without acute liver failure. Cumulative amounts of free carnitine, medium- or long-chain species in excess of the 95th percentile of the control group were considered abnormal. Fourteen samples had normal profiles. Three had markedly elevated concentrations of free carnitine, whereas ten showed elevations in medium- or long-chain species. The relative risk of death was 2.86 (95% confidence interval, 1.08-7.54, P = .01) in the 10 children with elevated concentrations of medium- or long-chain species compared with those with normal analyses. Overall, medium- and long-chain acylcarnitines were increased in those patients who died compared with survivors, (dead vs. alive; medium-chain, 187 +/- 74 vs. 32 +/- 12 micromol/L, P = .008; long-chain, 146 +/- 74 vs. 15 +/- 8 micromol/L, mean +/- standard error of the mean, P = .018). These studies describe biliary free and esterified carnitine profiles in children with acute liver failure. In conclusion, the findings raise the hypothesis that abnormalities in fatty acid oxidation may predispose to a worse outcome in acute liver failure.
Power and sideband studies of a Raman FEL

Abstract Power and spectral measurements are reported from the Columbia Raman Free Electron Laser experiment. High power pulsed radiation (4 MW, 100 ns) is obtained at wavelength ∼ 2 mm, using a 750 kV electron beam with high current density and very small ( 1 2 % ) momentum spread. We show the development of high power sidebands as the undulator pump field is increased, and discuss a mechanism for control of the sideband wavelength. The FEL, configured as an oscillator, has been operated with both constant and variable period undulators.
Normal-mode refinement of anisotropic thermal parameters for potassium channel KcsA at 3.2 A crystallographic resolution

Summary We report a normal-mode method for anisotropic refinement of membrane-protein structures, based on a hypothesis that the global near-native-state disordering of membrane proteins in crystals follows low-frequency normal modes. Thus, a small set of modes is sufficient to represent the anisotropic thermal motions in X-ray crystallographic refinement. By applying the method to potassium channel KcsA at 3.2 A, we obtained a structural model with an improved fit with the diffraction data. Moreover, the improved electron density maps allowed for large structural adjustments for 12 residues in each subunit, including the rebuilding of 3 missing side chains. Overall, the anisotropic KcsA structure at 3.2 A was systematically closer to a 2.0 A KcsA structure, especially in the selectivity filter. Furthermore, the anisotropic thermal ellipsoids from the refinement revealed functionally relevant structural flexibility. We expect this method to be a valuable tool for structural refinement of many membrane proteins with moderate-resolution diffraction data.
Rapid and precise method for analysis of energy dispersive X-ray spectra

A new, precise, and rapid method for the analysis of energy dispersive x-ray spectra generated by electron beam or x-ray excitation is presented. It includes the use of Gaussian profiles and a polynomial of I/E (where E is the x-ray energy) to represent the observed x-ray characteristic lines and background, automatic sectioning of the entire spectrum, and a figure of merit to estimate goodness of fit. Details of the method and its programming techniques are given. Results of analyzing complicated energy dispersive x-ray (EDX) spectra of multi-element alloys are presented.
Coring-related deformation of Leg 208 sediments from Walvis Ridge: Implications for paleomagnetic data

Abstract Both shipboard and shore-based magnetic studies of Ocean Drilling Program (ODP) Leg 208 sediments produced poor-quality directional data. A noisy inclination signal and a pervasive declination bias demonstrate that the sediments had been remagnetized and/or deformed. In an attempt to characterize any deformation, we carried out anisotropy of magnetic susceptibility (AMS) experiments on a suite of samples from Sites 1262 and 1267. Results show that the cores have suffered at least two kinds of deformation, one producing a tilting of the foliation (by up to 40° from horizontal in some intervals), and the other producing a lineated fabric. The former is firmly linked to lithology – higher carbonate content results in a higher degree of tilting – while the latter may be more closely tied to depth, suggesting the two fabrics result from different processes. The remanence directions show no obvious correlation to either fabric, suggesting that some third mechanism may have remagnetized the sediments, possibly an isothermal remanence acquired during the drilling process. In this study, the severity of the deformation may be linked to the high carbonate content of the cores, but pinpointing precise causes for both the AMS fabric and the directional anomalies remains elusive. It is clear, however, that the deformation is complex, pervasive and has significant implications for the interpretation paleomagnetic data from Leg 208.
Matrigel influences morphology and cathepsin B distribution of prostate cancer PC3 cells

Increases in expression and activity of matrix-degrading enzymes such as the cysteine proteinases cathepsins B and L, and abnormal levels of their inhibitors, the cystatins, are associated with tumor cell invasion and metastasis. Environmental conditions have been shown to be causative factors in the development of a metastatic/invasive phenotype. We hypothesized that cell-matrix interactions affect the expression and activity of cathepsins B and L and their inhibitors in the prostate cancer cell lines, PC3 and DU145. To test this possibility, PC3 and DU145 were plated on uncoated surfaces or on surfaces coated with the reconstituted basement membrane, Matrigel. The cells were analyzed for cathepsins B and L immunolocalization, protein expression and activity 48 h after plating. Our data demonstrated that cathepsins B and L displayed a distinct punctate distribution with little co-localization; individual cells displayed a predominant staining for one or the other enzyme. Cathepsin B had a perinuclear distribution in PC3 grown on uncoated surfaces but a more peripheral staining in PC3 plated on Matrigel. Localization of cathepsin L remained predominantly perinuclear regardless of the plating surface. In addition to the translocation of cathepsin B from a perinuclear distribution to the cell periphery, growth of PC3 on Matrigel shifted cathepsin B activity from the cell extract to the media. There were no significant changes in cathepsins B and L immunolocalization or activity in DU145 with regard to plating surfaces. Likewise, the activity of endogenous cysteine proteinase inhibitors (CPIs) and protein expression of cystatin C remained unchanged in both cell lines. In conclusion, the interaction of PC3 prostate cancer cells with extracellular matrix components affects the distribution of cathepsin B protein and activity.