cssi/SciSciGPT-SciSciNet huggingface dataset:
PARP-1 Regulates Resistance of Pancreatic Cancer to TRAIL Therapy

Purpose: Activating extrinsic apoptotic pathways targeting death receptors (DR) using agonistic antibodies or TNF-related apoptosis-inducing ligand (TRAIL) is promising for cancer therapy. However, most pancreatic cancers are resistant to TRAIL therapy. The present studies aimed to identify combination therapies that enhance the efficacy of TRAIL therapy and to investigate the underlying mechanisms. Experimental Design: A xenograft model in nude mice was used to determine pancreatic cancer tumorigenesis and therapeutic efficacy of TRA-8, a monoclonal agonistic antibody for DR5. Pancreatic cancer cells were used to characterize mechanisms underlying PARP-1 regulation of TRA-8–induced apoptosis in vitro . Results: PARP-1 was found highly expressed in the TRA-8–resistant PANC-1 and Suit-2 cells, compared with TRA-8–sensitive BxPc-3 and MiaPaca-2. Inhibition of PARP-1 with a pharmacologic inhibitor sensitized PANC-1 and Suit2 cells to TRA-8–induced apoptosis in a dose-dependent manner. Furthermore, siRNAs specifically knocking down PARP-1 markedly enhanced TRA-8–induced apoptosis in vitro and augmented the efficacy of TRA-8 therapy on tumorigenesis in vivo . PARP-1 knockdown increased TRA-8–induced activation of caspase-8 in the death-induced signaling complex (DISC). Immunoprecipitation with DR5 antibody identified the recruitment of PARP-1 and PARP-1–mediated protein poly-ADP-ribosylation (pADPr) modification in the DR5-associated DISC. Further characterization revealed that PARP-1–mediated pADPr modification of caspase-8 inhibited caspase-8 activation, which may contribute to its function in regulating TRA-8 resistance. Conclusions: Our studies provide molecular insights into a novel function of PARP-1 in regulating the extrinsic apoptosis machinery and also support interventions combining PARP-1 inhibitors with DR agonists for pancreatic cancer therapy. Clin Cancer Res; 19(17); 4750–9. ©2013 AACR .
TSV defects and TSV-induced circuit failures: The third dimension in test and design-for-test

3D integrated circuits (3D ICs) based on through-silicon vias (TSVs) have emerged as a promising solution for overcoming interconnect and power bottlenecks in IC design. However, testing of 3D ICs remains a significant challenge, and breakthroughs in test technology are needed to make 3D integration commercially viable. This paper first presents an overview of TSV-related defects and the impact of TSVs in the form of new defects in devices and interconnects. The paper next describes recent advances in testing, diagnosis, and design-for-testability for 3D ICs and techniques for defect tolerance using redundancy and repair. Topics covered include various types of TSV defects, stress-induced mobility and threshold-voltage variation in devices, stress-induced electromigration in inter-connects, pre-bond and test-bond testing (including TSV probing), and optimization techniques for defect tolerance.
THE EFFECT OF ETHANOL ON HEPATIC FATTY ACID SYNTHESIS.

Abstract It has been demonstrated that a single oral dose of ethanol will elevate the triglyceride content in rat liver (1). However, there is no agreement on the mechanism of this effect. Lieber and Schmid have presented data which suggests that ethanol increases the incorporation of C-14 labelled acetate in vivo or in vitro into long chain fatty acids of rat liver (2,3). These workers have proposed that the increased NADH which is generated by ethanol oxidation stimulates fatty acid synthesis. Data by other workers, however, have not confirmed these results (4,5,6). In addition, Bortz et al (7) have shown that the rate of incorporation of acetate into long chain fatty acids in the liver is controlled by the acetyl-CoA-carboxylase catalyzed reaction: This reaction precedes the reductive steps in the fatty acid synthetase system (reaction 2), during which the reduced pyridine nucleotides produced by ethanol oxidation would be used. Reaction 1 can be selectively inhibited by feeding animals a fatty meal or by starvation (7,8). Under these conditions it should be possible to test whether ethanol can drive the over-all rate of lipogenesis by a mass action effect on reaction 2. In addition some information on the influence of ethanol on reaction 1 under these conditions may be obtained. Accordingly, we have investigated the effect of ethanol on lipogenesis in the livers of animals which have been either fed a fatty meal or have been fasted.
Beyond tissue plasminogen activator: Mechanical intervention in acute stroke☆☆☆★

Mechanical interventions in acute ischemic stroke promise to provide emergency physicians with tools to treat patients in whom conventional thrombolysis might be ineffective or contraindicated, including most patients with stroke who arrive at the emergency department beyond the 3-hour time window for intravenous tissue plasminogen activator. A systematic MEDLINE literature review was performed. Endovascular interventions currently in early human clinical trials include the use of lasers, ultrasonography, angioplasty, microsnares, and a variety of clot-retrieval devices. Potential advantages of these approaches include more rapid recanalization of occluded vessels, reduced or no exposure to fibrinolytic agents, and a longer treatment window. Early safety trials are promising, with serial improvements in device design to minimize trauma to cerebrovascular endothelium and accelerate vessel recanalization. The purpose of this review is to provide the emergency medicine community with an understanding of these promising and emerging approaches to acute stroke therapy.
The order of the remainder in derivatives of composition and inverse operators for p-variation norms

The theory of differentiable statisticals began with work of von Mises [e.g., von Mises (1936, 1947) and Filippova (1961)]. A nonlinear funtional T is defined, for examble, on distribution functions.Von Mises differentiated T at a distribution funtion F along lines. For T to have a (Gâteaux) derivative at F means that, in the direction of a function h, $$T(F + th) = T(f) + tT^\prime(F)(h) + 0 (|t|) \quad {\rm as} \; t\rightarrow 0.$$ (1.1) Here \(T^\prime(F)(.)\) is a bounded linear operator on funtions h, for example, of the form $$T^\prime(F) (h) = \int g \quad dh \hbox{for some function} g (\hbox{depending on} F).$$ (1.2)
Neurofibromatosis 1 and 2

Neurofibromatosis (NF) 1 and 2 are multisystem disorders associated with a variety of neoplastic and non-neoplastic manifestations that typically progress in severity during the lifetime of the affected patient. The importance of appropriately diagnosing these disorders stems from the fact that the natural history of an associated neoplasm, such as a peripheral nerve tumor or an optic glioma, may be significantly different depending on whether or not the lesion arises in a person with NF. In addition, the indications for therapeutic intervention, hierarchy of treatment options and long-term management goals may differ substantially for patients with NF-related versus sporadic tumors. Finally, recognition of the diagnosis comprises an essential step for providing appropriate multidisciplinary evaluation and counseling to affected patients and their families. This article addresses the principal manifestations of these disorders and provides a contemporary review of the diagnostic and therapeutic issues that arise in children with NF1 and NF2.
Serine 318 Is Essential for the Pyrimidine Selectivity of the N2 Na+-Nucleoside Transporter

Molecular cloning has isolated two subtypes of Na+-nucleoside transporters; one is pyrimidine-selective (N2), and the other is purine-selective (N1). Using chimeric rat N2/N1 transporters, we previously demonstrated that transmembrane domains (TM) 8 and 9 are the major sites for substrate binding and discrimination. Interestingly, when TM8 of N2 was replaced by that of N1, the resulting chimera, T8, lost the pyrimidine selectivity of N2 and accepted both purine and pyrimidine nucleosides. Five residues differ between rat N2 and N1 in TM8. To identify the critical residues responsible for transport selectivity, the five residues in N2 were systematically changed to their equivalents in N1. Replacing the serine residue at position 318 to its equivalent N1 residue, glycine, caused N2 to lose its selectivity for pyrimidine nucleosides and accept purine nucleosides as substrates. In contrast, replacing the other four residues did not change the pyrimidine selectivity of N2. Furthermore, when glycine 318 in chimera T8 was changed back to serine, the chimeric transporter regained pyrimidine selectivity. These observations suggest that serine 318 is located in the nucleoside permeation pathway and is responsible for the substrate selectivity of N2. An adjacent residue, glutamine 319, was found to be important in modulating the apparent affinity for nucleosides.
Solid‐Phase Microextraction (SPME) of Pyrazines in Model Reaction Systems

Headspace solid-phase microextraction (HS-SPME) combined with gas chromatography (GC) was used for isolating and analysing pyrazines formed in a model system. This system consisted of an aqueous mixture of glucose, glycine and sodium hydroxide. Pyrazine formation was accelerated by heating in a microwave oven. Results were compared with our earlier ones using conventional techniques for isolation of pyrazines. HS-SPME-GC showed several advantages over traditional methods. The method is rapid, sensitive, easy to use and reproducible. Headspace and liquid of the model reaction were extracted and the results obtained using headspace sampling showed good agreement with the methylene chloride extraction method. In all cases, coefficients of variation of 5% or lower were obtained when the SPME extraction time was consistent.
Texas Has a New Pathotype of Peronosclerospora sorghi, the Cause of Sorghum Downy Mildew.

Three pathotypes of Peronosclerospora sorghi were known to occur in Texas as of 1980, with pathotype 3 (P3) predominant on sorghum (Sorghum bicolor) grown in the Upper Coast area. Following the use of hybrids resistant to P3, combined with metalaxyl or mefenoxam seed treatment, sorghum downy mildew (SDM) became a minor disease in Texas until the occurrence of a widespread outbreak caused by a P3 strain resistant to metalaxyl and mefenoxam in Wharton County in 2001 (2). During July 2004, <1% of plants in a commercial field in Wharton County planted to two Pioneer Brand P3-resistant hybrids had white stripes on the leaves and leaf shredding typical of systemic SDM. To obtain inoculum for pathogenicity studies, several infected plants were removed from the field and transplanted to pots for growth in a greenhouse. Systemically infected leaves suitable for inoculum production subsequently developed from tillers. Conidia were collected from leaves using a tiered temperature system (1). One-week-old seedlings o...
Review of quantitative standards and guidelines for fungi in indoor air

Existing quantitative standards/guidelines for fungi in indoor air issued by governmental agencies are based primarily on baseline data (rather than health effects data), and are either absolute (numerical) or relative (indoor/outdoor comparisons) or a combination of the two. The Russian Federation is the only governmental agency that has binding quantitative regulations for bioaerosols. Recommended guidelines have been proposed or sponsored by North American and European governmental agencies and private professional organizations. A considerable number of frequently cited guidelines have been proposed by individuals based either on baseline data or on personal experience. Quantitative standards/guidelines range from less than 100 CFU/m3 to greater than 1000 CFU/m3 (total fungi) as the upper limit for non-contaminated indoor environments. Major issues with existing quantitative standards and guidelines are the lack of connection to human dose/response data, reliance on short term grab samples analyzed only by culture, and the absence of standardized protocols for data collection, analysis, and interpretation. Urgent research needs include the study of human responses to specific fungal agents, development and widespread use of standard protocols using currently available sampling methodologies, and the development of long term, time-discriminating personal samplers that are inexpensive, easy to use, and amenable to straightforward, relevant analysis.
A review of physical and kinetic models of thermal degradation of expanded polystyrene foam and their application to the lost foam casting process

Abstract A review of the literature was conducted in search of an appropriate kinetic model applicable to the polystyrene foam decomposition phenomena encountered in the lost foam casting process. A brief review of the models describing the physical process of foam degradation is also presented. During this investigation, various kinetic models describing polystyrene thermal decomposition in the plastics recycling process have been reviewed. The review indicates that the process conditions in which these models were developed were very different from the casting process conditions, and hence no one model could be suitably employed for the latter. The authors suggest that a more rigorous and intrinsic kinetic experiment depicting the actual foundry conditions is necessary to develop a model that describes the foam degradation kinetics.
On Saint-Venant Torsion and the Plane Problem of Elastostatics for Multiply Connected Domains

Michell [1] (1899), in a classical paper, showed that the determination of the plane-strain and generalized plane-stress solutions associated with the three-dimensional plane traction-problem of the linearized equilibrium theory of homogeneous and isotropic elastic solids—in the absence of body forces—is reducible to a Dirichlet problem for the two-dimensional biharmonic equation on the cross-sectional domain at hand.1 This reduction is achieved with the aid of a general solution of the two-dimensional stress equations of equilibrium in terms of Airy’s stress function. That the generating Airy function must be biharmonic follows from the requirement that the corresponding strains satisfy the appropriate compatibility condition, while the accompanying boundary data for the Airy function and its normal derivative result from an integration of the original boundary conditions for the given surface tractions.
The development of pattern recognition ability in children

Abstract Pattern recognition development was studied in high and low ability preschool, kindergarten, and first-grade youngsters. Pattern recognition was assessed by the administration of 96 pattern tasks which measured the ability of a youngster to find: (a) duplicate patterns and elements to a model; (b) the opposite pattern to a model; and (c) duplicate patterns but different elements than in the model. Aside from main effects for grade level, ability level, and pattern task, a significant three-way interaction was noted. This interaction was analyzed in terms of its component simple effects. The implication of these simple interaction effects for Piagetian theory and educational practice were discussed.
Clinical Ethics and Happiness

Most contemporary accounts of clinical ethics do not explain why clinicians should be ethical. Those few that do attempt an explanation usually claim that clinicians should be ethical because ethical behavior provides an important good for the patient--better care. Both these approaches ignore the customary traditional reason for being ethical, namely, the good of the moral agent. This good was commonly called 'happiness'. The following article shows how the personal happiness of the moral agent provided a major reason for being ethical in the ancient philosophical and biblical traditions and how it continues to play a role in the more modern rights-based, Kantian and utilitarian theories. This history suggests that the personal happiness of the clinician, rightly understood, is a legitimate and important goal of clinical ethics.
Design of the LAMPF Low-Energy Pion Channel☆

Abstract The optical design of the LAMPF Low-Energy Pion Channel is presented, and the results of calculations made to determine the beam characteristics are reviewed. Those aspects of the channel mechanical design which are somewhat unique are described.
Ethnobotany of the Naranjilla (Solanum quitoense) and its relatives

One of my former students, who happens to be here tonight, some time ago suggested that instead of giving one of my interesting, humorous and entertaining talks I should use the occasion to say something significant, if not profound. That was a difficult assignment, but I did give it some consideration. I thought of speaking on the food problems of the world, but I decided against it for two reasons. First, I think that as economic botanists you should be well aware of the problems and that you also realize that we are in a position to offer some solutions. Maybe a single individual can do very little, but collectively I think we could have an impact. The second reason is that I feel that after eating the way we have tonight, it would be embarrassing to say more than I already have on this subject. So I am going to compromise. I hope the subject is neither too light nor too ponderous and hence suitable for the occasion. I thought that I would try to convey to you, by using some of my own research, why I find ethnobotanic research so fascinating and how it may at times take some unusual turns. I used the word ethnobotany in my title although I realize that this is an economic botany meeting. Perhaps I should try to distinguish between ethnobotany and economic botany. Ethnobotany may be defined as the study of plants in relation to people. Obviously it is a very broad field, including many, if not all, aspects of botany, and many other disciplines as well. Economic botany, on the other hand, usually concerns such subjects as the production, distribution and consumption of plants useful to people. Some (for example, Maheshwari, 1983) would limit ethnobotany to the use of plants by "primitive" human societies; economic botany, therefore, would concern plants and modern human societies. I, however, would prefer to think of ethnobotany as comprising both fields, and that perhaps economic botany is then a subdivision of ethnobotany that is involved where money becomes an important consideration. At the same time I feel we might also think of it as botany in the service of humankind today.
Measurements and inverse calculations of spectral radiation intensities of a turbulent ethylene/air jet flame

Abstract Fast (6250 Hz) line-of-sight measurements of infrared spectral radiation intensities ( I λ ) from a luminous flame and a new deconvolution technique for the estimate of local scalar properties using inverse radiation calculations are reported. Time series data of I λ for one diametric and nine chord-like radiation paths in a representative horizontal plane were measured. Statistical properties of I λ , including mean, root mean square (rms), probability density function, autocorrelation coefficient, and power spectral density, were obtained from the time series data. The measured statistical properties of I λ at two representative wavelengths, which are dominated by carbon dioxide (CO 2 ) and soot radiation, respectively, are reported. The autocorrelation coefficient data show large negative loops with repeatable zero crossings at 20 ms and minimum values as low as −0.2 at 30–40 ms. Radial distributions of mean and rms CO 2 mole fractions and temperatures were estimated using inverse calculations of mean I λ at two different wavelengths dominated by CO 2 radiation in conjunction with the relationship of these quantities to mixture fractions. Soot volume fraction distributions were also estimated using inverse calculations of mean I λ at a wavelength dominated by continuum soot radiation. The estimated local mixture fraction distributions were in reasonably good agreement with sampling data from similar flames. The calculated mean I λ from 1.4 to 4.8 μm other than those used in the inverse calculations matched the experimental data well. The present method provides non-intrusive measurements of major gas species and temperature statistics in turbulent soot containing flames not accessible to other optical diagnostics.
Chemical processes in Triton's atmosphere and surface

The Neptune moon Triton may have an appreciable atmosphere; the preliminary calculations of Delitsky (1983) have suggested that there should be a significant resultant chemistry in a possible N2 ocean with dissolved CH4, given charged-particle radiolysis of gaseous mixtures and gamma radiolysis of N2-CH4 solutions. The latter will yield substantial quantities of organic products which will be partially soluble in any N2-CH4 liquid present. Attention is presently given to the energy sources available for Triton, in order to estimate rates of synthesis and ascertain the possible history of such simple and complex organic products on Triton's surface.
Perioperative cyclooxygenase 2 inhibition to reduce tumor cell adhesion and metastatic potential of circulating tumor cells in non–small cell lung cancer

Objective Surgical manipulation of lung cancers may increase circulating tumor cells and contribute to metastatic recurrence after resection. Cyclooxygenase 2 is overexpressed in most non–small cell lung cancer and upregulates the cell adhesion receptor CD44. Our goal was to examine the effects of perioperative cyclooxygenase blockade on the metastatic potential of circulating tumor cells, CD44 expression, and adhesion of cancer cells to extracellular matrix. Methods Human non–small cell lung cancer cells (A549) were injected through the lateral tail vein in an in vivo murine model of tumor metastasis with three random treatment groups: no treatment, perioperative selective cyclooxygenase 2 inhibition (celecoxib) only, and continuous celecoxib. Lung metastases were assessed at 6 weeks by a blinded observer. For in vitro experiments, cells were treated with celecoxib, and expression of CD44 was determined by Western blotting. Extracellular matrix adhesion was assessed by Matrigel (BD Labware, Bedford, Mass) assay. Results In vivo lung metastases were significantly decreased relative to control by both perioperative and continuous celecoxib ( P = .0135). There was no significant difference in number of metastases between continuous and perioperative treatment groups. In vitro adhesion to the extracellular matrix was significantly inhibited by celecoxib in a dose-dependent manner ( P Conclusion Celecoxib significantly reduced establishment of metastases by circulating tumor cells in a murine model. It also inhibited CD44 expression and extracellular matrix adhesion in vitro. Perioperative modulation of cyclooxygenase 2 may be a novel strategy to minimize metastases from circulating tumor cells during this high-risk period.
Forcing closed unbounded subsets of ω2

Abstract It is shown that there is no satisfactory first-order characterization of those subsets of ω2 that have closed unbounded subsets in ω1,ω2 and GCH preserving outer models. These “anticharacterization” results generalize to subsets of successors of uncountable regular cardinals. Similar results are proved for trees of height and cardinality κ+ and for partitions of [κ+]2, when κ is an infinite cardinal.
Hydrodynamic measurements for imperfect mixing processes: Newtonian Fluids

The response of a continuous flow mixing system to a step change in an input variable is discussed from the standpoint of dimensional analysis. This idea is presented as an alternative to using zone models for predicting residence time distributions in systems where imperfect mixing occurs. Mixing experiments were performed in a cylindrical flat bottomed tank geometrically similar to tanks commonly used for industrial processes. The response of the system to a step change in feed concentration was observed. Initially the tank contained a salt solution. At the start of an experiment, a stream of salt-free diluent was introduced at the top of the tank and a stream of the salt solution was drained from the bottom, keeping the liquid volume in the tank constant. The salt concentration in the output stream was measured continuously after the start of the experiment. The experimental results are correlated in terms of dimensionless variables, and the variables affecting the mixing process most strongly are determined. The results show that variations in throughput rate or in impeller shape or rotational speed affect the mixing process much more than does impeller position. The data are also compared with models proposed by other authors, and the model constants are evaluated.
Anti-Streptococcus mutans ribosome monoclonal antibodies recognize a cell surface antigen on different serotypes

We have produced a panel of murine monoclonal antibodies to a ribosomal preparation fromStreptococcus mutans NCTC 10449 (serotypec). Ribosomal preparations were isolated from homogenized cells by differential centrifugation and consisted of approximately 17% protein and 83% RNA. Splenocytes from immunized animals were fused to NS-1 myeloma cells using polyethylene glycol and dimethyl sulfoxide. Four stable hybridomas have been currently established, two of which secrete the IgG-k isotype and the other two the IgM-k isotype. All of the monoclonal antibodies react with wholeS. mutans cells representing different serotypes, while not with other bacteria. In Western blot analysis of the ribosomal preparation resolved by one-dimensional electrophoresis, the nmonoclonal antibodies recognize a specific component with an apparent molecular weight of 65,000. These results indicate that theS. mutans ribosomal preparation contains an immunogenic site that is serologically indistinguishable from a species-specific surface determinant common to different serotypes.
HOLE-BURNING SUBTRACTED FLUORESCENCE LINE-NARROWING SPECTROSCOPY OF SQUARAINES IN POLYMER MATRICES

We present vibrationally resolved line-narrowed fluorescence spectra of seven centrosymmetric squaraines in polyethylene and polystyrene matrices at 1.4 K. At a fixed excitation frequency, the inte...
X-rays from Coalescing Atoms

The discovery and investigation of X-ray continua has provided a new tool for studying the detailed electronic processes that occur when atoms collide. In the collisions considered here, the quasimolecular origin of the continuum radiation has been established. Therefore, as the atomic numbers of the projectiles and target atoms are increased one can simulate some of the properties of superheavy atoms. In particular, the peaked nature of the x-ray energy dependence of the anisotropy of K, L, and M MO radiation, as well as the peaked nature of the M MO spectra, will allow approximate spectroscopic studies of superheavy atoms. Special excitement attaches to the possibility of observing fundamental processes occurring under extremely high electric and magnetic fields. The recent successful development of a 1400-Mev U beam at the GSI (Gesellschaft fur Schwerionenforschung) accelerator in Darmstadt, Germany, promises an imminent attack on these basic problems (63).
Silsesquioxanes as synthetic platforms. Thermally curable and photocurable inorganic/organic hybrids

We report here the synthesis and characterization of simple methacrylate/cube hybrids trhat can act as thermosets or photocurable monomers. These materials are easily manipulated, yet retain very high masked silica loadings
Electrochemical Noise Analysis of Iron Exposed to NaCl Solutions of Different Corrosivity

Potential and current noise data have been collected for pure iron foils which were exposed to 0.5N which was aerated, deaerated, or aerated with added as inhibitor. Data were obtained at the beginning of each hour over a 24 h period. The noise data were displayed as power spectral density plots or as the rms values of potential and current . The potential noise data seem to be affected by fluctuations of mass transport and did not agree with the known corrosion behavior of the systems under investigation. However, good agreement was observed for the current noise data. For the noise resistance similar values as for the polarization resistance determined with EIS at the end of the tests were obtained. The pit index defined by others as , where is the mean current in a noise measurement, did not provide meaningful information. The experimental data obtained in this investigation have been compared with those reported previously by Lumsden et al.
Less is more: Two- and three-dimensional graphics for data display

Psychologists tend to rely on a few simple graphs for presenting their results. The line chart, scatterplot, and profile plot have their uses, but there are new methods for displaying data which can reveal more. This paper shows several univariate and multivariate displays which can be created on a desktop computer and which reveal the distribution of the data they summarize.
On Tensor Forces and the Theory of Light Nuclei

The quadrupole moment of the deuteron indicates the existence of non-central tensor forces in nuclei which destroy the constancy of the total orbital angular momentum. With simple operational representations of the wave functions, the influence of two-body tensor forces on the ground state eigenfunctions of the light nuclei ${\mathrm{H}}^{3}$ and ${\mathrm{He}}^{4}$ has been calculated. In ${\mathrm{H}}^{3}$ the tensor forces directly couple to the fundamental $^{2}S_{\frac{1}{2}}$ state a $^{4}D_{\frac{1}{2}}$ state, which in turn interacts with $^{2}P_{\frac{1}{2}}$ and $^{4}P_{\frac{1}{2}}$. To the fundamental $^{1}S_{0}$ state of ${\mathrm{He}}^{4}$ is admixed a $^{5}D_{0}$ state which is coupled by the tensor forces with $^{3}P_{0}$. All states consistent with the total angular momentum and parity conservation rules occur in the ground state eigenfunctions, and these nuclei therefore constitute the simplest examples of the complete break-down of spin and orbital angular momentum conservation laws. Rarita and Schwinger have satisfactorily accounted for the properties of the deuteron by including the tensor force in a simple interaction represented by a rectangular well potential. With this interaction to describe the forces between all pairs of nuclear particles, the binding energies of ${\mathrm{H}}^{3}$ and ${\mathrm{He}}^{4}$ have been estimated by a variation method The trial functions are of the form $^{2}S_{\frac{1}{2}}+^{4}D_{\frac{1}{2}}$ for ${\mathrm{H}}^{3}$ and $^{1}S_{0}+^{5}D_{0}$ for ${\mathrm{He}}^{4}$, with Gaussian radial functions. The calculations yield 32 and 50 percent of the binding energy for ${\mathrm{H}}^{3}$ and ${\mathrm{He}}^{4}$, respectively, while a similar test calculation for the deuteron gives 54 percent of the binding energy. The probability that these nuclei are in a $D$ state is found to be 4 percent for all three nuclei, in agreement with the exact deuteron computations. Improvement of the radial dependence of the trial functions increases the estimated binding energy of the deuteron to 76 percent of the known value but does not materially affect either the estimated binding energies of ${\mathrm{H}}^{3}$ and ${\mathrm{He}}^{4}$, or the amount of $D$ state admixture of the three nuclei. An analysis of the results shows that the tensor forces, which produce all the binding in the deuteron, are relatively ineffective in binding ${\mathrm{H}}^{3}$ and ${\mathrm{He}}^{4}$. This apparently indicates that the assumption of ordinary and tensor forces of the same range is not adequate to represent the properties of ${\mathrm{H}}^{3}$ and ${\mathrm{He}}^{4}$.
Cancer cachexia and the rate of whole body lipolysis in man

Abstract While malnutrition attending cancer cachexia may be associated with variable losses of body fat, lipid metabolism has been only minimally studied. To clarify potential aberrations of lipid metabolism in weight losing cancer patients, the whole body rate of lipolysis was determined in 9 cancer patients in the postabsorptive state and compared to that in 5 normal subjects. A primed-three stage infusion of glycerol was used to measure plasma glycerol clearance and turnover. A positive correlation between glycerol turnover and plasma concentration was demonstrated in both cancer patients (r = 0.72) and in normal subjects (r = 0.81). Glycerol turnover rate in cancer patients (2.05 ± 0.14 umol · kg−1 · min−1) was not different from that in normals (2.31 ± 0.50); while glycerol clearance in cancer patients (1.72 ± 0.13 L/min) was significantly lower (P
Variant angina pectoris: investigation of indexes of sympathetic nervous system function.

Abstract One thousand forty-five spontaneous episodes of S-T segment elevation were observed in three patients over a total of 72 days of continuous electrocardiographic monitoring. Eighty-nine percent of episodes were asymptomatic; chest pain tended to occur with episodes longer than 3 minutes, and ventricular ectopy occurred almost exclusively with symptomatic episodes. Nitroglycerin regularly relieved angina or S-T elevation, or both. Plasma and urinary catecholamines and their metabolites were normal. Episodes of variant angina were not associated with a generalized increase in sympathetic outflow because serum catecholamine levels at the onset and termination of the S-T abnormalities were not elevated. Controlled trials of propranolol showed no significant beneficial effect. Propranolol significantly increased the length of episodes of S-T elevation in one patient, increasing ventricular irritability. The overall course of variant angina was quite variable, with spontaneous and long-lasting remissions, necessitating cautious interpretation of clinical trials.
Fluorescence Excitation–Emission Features of Aflatoxin and Related Secondary Metabolites and Their Application for Rapid Detection of Mycotoxins

The persistent occurrence of aflatoxins in food and feed remains a problem for producers of commodities subject to colonization with toxigenic molds. Aflatoxins are secondary metabolites of fungi of the Aspergillus spp. associated with deleterious health effects. Because current screening methods for these toxins are lengthy, destructive, and costly, there is a continuous search for a more rapid, noninvasive, and cost-effective technology. The present study utilized a fluorescence excitation–emission matrix (EEM) of aflatoxin as well as two additional secondary metabolites (kojic acid and the bright greenish-yellow fluorescence (BGYF) compound) of Aspergillus flavus measured with a fluorescence spectrophotometer. The results were compared to image data acquired with a fluorescence hyperspectral sensor in order to evaluate the potential of image-based technology for detecting aflatoxin in grain. The excitation–emission matrix of aflatoxin B1 standard produced overlapping peaks in 340–400 nm of excitation range emitting in the blue range at around 450 nm. The spectral signature extracted from the hyperspectral image was also in the blue range, emitting blue fluorescence. Because the results from both systems were comparable, where all fluorescence peaks were in the blue range, the present study validates the feasibility of image-based technology for nondestructive detection of aflatoxin in corn. Additional peaks were revealed in the aflatoxin EEM in the 260-nm excitation range that were not present in the kojic acid and BGYF compound mixture. This new information allows for the separation of the aflatoxin signature from the potentially confounding overlap of other secondary metabolites occurring in the blue and blue-green spectral ranges.
PDE4 inhibition: a novel approach for the treatment of inflammatory bowel disease

Inflammation is a hallmark of inflammatory bowel disease (IBD), and elevation of cAMP levels can inhibit the pro-inflammatory and tissue-destructive properties of leukocytes. Phosphodiesterase 4 (PDE4) is the predominant enzyme that metabolizes cAMP in inflammatory cells, and the anti-inflammatory and immunomodulatory potential of PDE4 inhibitors in human leukocytes, endothelium and epithelium is well documented. Although PDE4 inhibitors have been investigated as treatments for several inflammatory diseases, this has focused mainly on asthma and chronic obstructive disease (COPD). Historically, their clinical utility has been limited by nausea and emesis. However, the PDE4 inhibitors cilomilast and roflumilast have recently shown efficacy in asthma and COPD, with a reduced propensity to cause nausea and emesis. In this review, we summarize for the first time the evidence that PDE4 inhibitors might have therapeutic benefit in IBD, and discuss mechanisms of action beyond the inhibition of inflammatory cells.
PROTEASE FOOTPRINTING ANALYSIS OF TERNARY COMPLEX FORMATION BY HUMAN TFIIA

Transcription factor (TF) IIA performs two important regulatory functions during RNA polymerase II transcription: it is required for efficient binding of TFIID to a core promoter and it mediates the effects of upstream activators, both through direct interaction with the TATA box binding protein (TBP). To begin studying how TFIIA mediates these effects, we used a highly sensitive protease footprinting methodology to identify surfaces of human TFIIA participating in TFIIA·TBP·TATA ternary complex formation. Chymotrypsin and proteinase K cleavage patterns of TFIIA bearing a 32P-end-labeled γ subunit revealed that amino acids 59-73 were protected from cleavage both in the context of an immobilized ternary complex and in a binary complex with TBP alone. In contrast, amino acids 341-367 in the β portion of a 32P-labeled α-β subunit were protected in the ternary but not in the binary complex, implying that those residues interact with promoter DNA. The regions of human TFIIA identified by protease footprinting are homologous to and encompass the yeast TFIIA residues that contact TBP and DNA in the recently solved crystal structure of the yeast ternary complex. The conservation of the regions and residues mediating complex formation implies that yeast and human TFIIA employ the same mechanism to stabilize the binding of TFIID to a core promoter.
Community walking programs for treatment of peripheral artery disease

Background Supervised walking programs offered at medical facilities for patients with peripheral artery disease (PAD) and intermittent claudication (IC), although effective, are often not used due to barriers, including lack of reimbursement and the need to travel to specialized locations for the training intervention. Walking programs for PAD patients that occur in community settings, such as those outside of supervised settings, may be a viable treatment option because they are convenient and potentially bypass the need for supervised walking. This review evaluated the various methods and outcomes of community walking programs for PAD. Methods A literature review using appropriate search terms was conducted within PubMed/MEDLINE and the Cochrane databases to identify studies in the English language that used community walking programs to treat PAD patients with IC. Search results were reviewed, and relevant articles were identified that form the basis of this review. The primary outcome was peak walking performance on the treadmill. Results Ten randomized controlled trials examining peak walking outcomes in 558 PAD patients demonstrated that supervised exercise programs were more effective than community walking studies that consisted of general recommendations for patients with IC to walk at home. Recent community trials that incorporated more advice and feedback for PAD patients in general resulted in similar outcomes, with no differences in peak walking time compared with supervised walking exercise groups. Conclusions Unstructured recommendations for patients with symptomatic PAD to exercise in the community are not efficacious. Community walking programs with more feedback and monitoring offer improvements in walking performance for patients with claudication and may bypass some obstacles associated with facility-based exercise programs.
The Interaction Between Role Structures and Self-Conceptions in Fostering Different Types of Self-Esteem in Innovative and Traditional Elementary Schools*

A two-dimensional model of inner and outer self-esteem is discussed wherein inner self-esteem is hypothesized to be an outcome of self-evaluations of performance in prominent role identities. Outer self-esteem is hypothesized to be related to self-evaluations of both prominent and nonprominent role identities. The research context is a comparison of the different processes facilitating self-esteem in innovative schools (emphasis on student-initiated activities and control) and traditional (emphasis on pre-determined curriculum and teacher-administrator control). Data across school type demonstrate a modest correlation between positive self-evaluations of performance in prominent role identities and both types of self-esteem. The data suggest that high evaluation of performance in nonprominent role identities is related to outer self-esteem but not to inner self-esteem. Further empirical clarification of the concepts was established by viewing the relationships within school type. In the innovative schools both types of self-esteem were predominantly related to positive evaluations of prominent role identities, whereas in the traditional schools both types of self-esteem were related to both performance in prominent and nonprominent role identities. Thus the theoretical distinction gained partial support while the process of gaining self-esteem was shown to be essentially different between alternate school structures. Controls for social desirability, race, sex, and father's occupation did not change these findings.
Estrogen receptors and cell signaling.

The Report by C. M. Revankar et al. (“A transmembrane intracellular estrogen receptor mediates rapid cell signaling,” 11 Mar., p. 1625) presents findings that the G protein-coupled receptor GPR30 localizes exclusively to endoplasmic reticulum and binds an estradiol-Alexa dye conjugate. As such,
The proposed role of neurotransmitter receptors in the pathophysiology of human myoclonic disorders

Abstract The hypothesis that central neurotransmitter receptor abnormalities are the basis of human myoclonic disorders is novel. Receptor abnormalities in any of several different neurotransmitter systems implicated in myoclonus may be genetic or the consequence of various brain injuries. These abnormalities might define pharmacologic subgroups of possible relevance to the clinical, neurophysiologic, and pathologic heterogeneity of myoclonus. Receptor abnormalities may be the primary pathophysiologic defect, involving the surface recognition site or effector-transducer mechanisms in the post-synaptic cell. Alternatively, changes in receptor density or affinity may be adaptive (recovery of function) or maladaptive (supersensitivity, subsensitivity, dysregulation). Drug treatments, then, could be targeted at the receptor changes, reversing abnormalities and enhancing compensatory mechanisms. Durrent therapy may inadvertently have such an effect. Polytherapy may be justified to target more than one component of the “pharmacologic receptor”. Identification of receptor abnormalities in human post-mortem brain may have diagnostic and therapeutic significance. New advances in the pharmacologic selectivity of receptor agonists and antagonists and in the measurement of receptors should be applied to the problem of myoclonus.
Synaptic pathology in retinoschisis knockout (Rs1-/y) mouse retina and modification by rAAV-Rs1 gene delivery

Purpose At an early age, the retinoschisin knockout (Rs1-KO) mouse retina has progressive photoreceptor degeneration with severe disruption of the outer plexiform layer (OPL) that decreases at older ages. The electroretinogram (ERG) undergoes parallel changes. The b-wave amplitude from bipolar cells is reduced disproportionately to the photoreceptor a-wave at young but not at older ages. The protein expression and morphology of the OPL in Rs1-KO mice was investigated at different ages, to explore the role of the synaptic layer in these ERG changes.
Stability and performance analysis of time delayed linear parameter varying systems with brief instability

LPV systems provide a systematic framework for the study of nonlinear systems by analyzing a representative family of linear time-invariant systems parameterized by some system parameters residing in compact set. The brief instability concept in such systems allows the linear system to be unstable for some values of the LPV parameters so that instability occurs only for short periods of time. The present paper extends the notion of brief instability to LPV systems with time delay in their dynamics. It provides tools for the stability and performance analysis of these systems, where performance is evaluated in terms of induced L2-gain (or so-called Hinfin norm). The main results of the paper illustrate that stability and performance conditions can be evaluated by examining the feasibility of parameterized sets of Linear Matrix Inequalities (LMIs). As an application of the derived analysis formulation, we use the interconnection of an LPV time delay system and a parameter-varying observer to estimate the outputs of the delayed system. The temporary loss of information arriving from sensors is taken into account to represent brief instability in the system. The numerical examples are used to illustrate the qualifications of the proposed analysis and synthesis conditions for loss of sensor data.
Improved spectral analysis of nearby tones using local detectors

This paper concerns the problem of resolvability power in the frequency domain. The canonical case of interest is to distinguish whether the received noise-corrupted signal is a single-frequency sinusoid or a two-frequency sinusoid, where the amplitudes, phases and frequencies are unknown to the receiver. Using a model-based hypothesis testing approach, we quantify a measure of attainable resolution between sinusoids with nearby frequencies, in the presence of noise. An explicit relationship is derived for the minimum detectable difference between the frequencies of two tones, for any particular false alarm and detection rate, and at a given SNR. An associated algorithm is proposed that produces significantly better performance compared to the standard subspace-based methods like MUSIC and can be effectively used in practice as a postprocessing step for the existing spectral estimation methods.
COMPARISONS OF MANAGERIAL AND EMPLOYEE SATISFACTION WITH A PERFORMANCE APPRAISAL SYSTEM

Questionnaires were administered to managers and employees in a large multinational corporation to assess satisfaction with various aspects of a performance appraisal system. Comparisons of managers' and employees' satisfaction were made by conducting factor analyses for each sample. The results indicate moderate similarity between the two groups. However, two significant differences were revealed by the analysis. First, there is evidence that employees perceive certain aspects of the appraisal system in a global way, whereas managers differentiate among various components and see them as distinct entities. Second, the relative importance of the factors differs between the two groups. The largest portion of variance accounted for in the employee sample pertained to general satisfaction with the system whereas for managers it pertained to the types of ratings made on the appraisal form. The results are discussed in terms of the different perspectives managers and employees have in the appraisal process.