cssi/SciSciGPT-SciSciNet huggingface dataset:
Characterization of skin abnormalities in a mouse model of osteogenesis imperfecta using high resolution magnetic resonance imaging and Fourier transform infrared imaging spectroscopy

Evaluation of the skin phenotype in osteogenesis imperfecta (OI) typically involves biochemical measurements, such as histologic or biochemical assessment of the collagen produced from biopsy-derived dermal fibroblasts. As an alternative, the current study utilized non-invasive magnetic resonance imaging (MRI) microscopy and optical spectroscopy to define biophysical characteristics of skin in an animal model of OI. MRI of skin harvested from control, homozygous oim/oim and heterozygous oim/+ mice demonstrated several differences in anatomic and biophysical properties. Fourier transform infrared imaging spectroscopy (FT-IRIS) was used to interpret observed MRI signal characteristics in terms of chemical composition. Differences between wild-type and OI mouse skin included the appearance of a collagen-depleted lower dermal layer containing prominent hair follicles in the oim/oim mice, accounting for 55% of skin thickness in these. The MRI magnetization transfer rate was lower by 50% in this layer as compared to the upper dermis, consistent with lower collagen content. The MRI transverse relaxation time, T2, was greater by 30% in the dermis of the oim/oim mice compared to controls, consistent with a more highly hydrated collagen network. Similarly, an FT-IRIS-defined measure of collagen integrity was 30% lower in the oim/oim mice. We conclude that characterization of phenotypic differences between the skin of OI and wild-type mice by MRI and FT-IRIS is feasible, and that these techniques provide powerful complementary approaches for the analysis of the skin phenotype in animal models of disease.
Supportive‐Expressive Therapy

The term “supportive-expressive psychoanalytic psychotherapy” (SET) was used originally to describe the open-ended, psychoanalytically oriented therapy conducted at the Menninger Foundation. One can trace SET's conceptual origins to Freud's technical papers and the works of several of his followers (e.g., Bibring, Fenichel, Stone). SET was formally manualized by Luborsky in the late 1970s (Luborsky, 1984) and has since that time been the focus of considerable research. This manualized version of SET is the focus of the present article. Keywords: psychodynamic therapy; psychoanalysis; empirically supported treatments; time-limited psychotherapy
Standing Orders in an Ambulatory Setting Increases Influenza Vaccine Usage in Older People

Objectives: To determine whether standing orders for influenza vaccine increase its usage in an ambulatory setting in elderly patients. Design: Retrospective analysis of influenza vaccine usage over 4 years (1999–2002). Setting: University ambulatory setting. Participants: Overall, 912 elderly patients of two physicians who issued standing orders and 884 elderly patients of two physicians who did not do so constituted the study group. Measurements: Physicians were categorized as to whether they issued a verbal or written standing order to their nurses to administer the influenza vaccine to patients aged 65 and older. Rates of influenza vaccination of patients whose physicians used standing orders were compared with those of physicians who did not use standing orders. Results: Five hundred seventy-six (63%) patients of physicians who used standing orders received influenza vaccine, compared with 332 (38%) patients of physicians who did not use them (P<.001). Standing orders accounted for a significantly higher rate of influenza vaccination in each study year. Moreover, in 2001, when influenza vaccine delivery was delayed, physicians who used standing orders maintained their same rate of usage, but physicians who did not had rates of about one-half their usage of the other 3 years. Conclusion: More Medicare recipients received influenza vaccine when their physicians used standing orders for its administration than when their physicians did not. Influenza vaccine represents an important prevention modality that demands widespread implementation, and standing orders can increase its usage.
Adaptive control of full information problem

Considers the adaptive output tracking problem in a state feedback configuration, with induced /spl Lscr//sub 2/ norm tracking objective. The authors' scheme does not guarantee the convergence of the estimated parameter, but the updated parameter vector /spl Theta/ is kept in the prescribed parameter set.
Atherosclerotic plaque segmentation at human carotid artery based on multiple contrast weighting MR images

The aims of this study are (1) to propose an image segmentation framework for multiple contrast weighting MR images; and (2) to analyze the agreement between segmentation results and histology sections. The proposed technique is actually based on the mean-shift density estimation algorithm and carefully designed to overcome the drawbacks in other existing methods. First, it has a very reliable and accurate initialization scheme that guarantees all potential clusters are within estimation. Secondly, the proposed method introduces a dynamic sphere mechanism that makes the mean-shift vector more reliable even with poor initialization. It can also enhance the accuracy of cluster center estimation when the searching processing is approaching the mode. Experimental results and comparison with histology sections demonstrate its encouraging performance. Moreover, the proposed approach can be easily extended to other general-purpose low-level image analysis problems.
Changing psychosocial morbidity in people aging with spinal cord injury.

OBJECTIVE to examine how scores on measures of stress, life satisfaction, depression, and psychological well-being relate to perceived quality of life among people with longstanding spinal cord injuries. DESIGN 189 members of a British population-based study of outcomes after spinal cord injury were evaluated at three-year intervals from 1990 to 1999. Participants rated their quality of life at each interval, and completed various psychosocial measures. Scores and results were analyzed to identify changes over time and correlations with perceived quality of life. RESULTS Self-ratings of quality of life were high and relatively stable over the duration of the longitudinal study. There were strong concurrent relationships between perceived quality of life and psychosocial outcomes. Across time periods, the outcomes studied did not seem to strongly predict later quality of life, but earlier perceived quality of life did predict later stress, depression, and psychological well-being. CONCLUSIONS Perceived quality of life among this group of individual with long duration spinal cord injuries was high and relatively stable over time. Significant relationships identified between earlier quality of life and later perceived stress, depression, and well-being suggest that quality of life, typically thought of as a key outcome may itself be a predictor of other outcomes.
PTEN regulates CD4+ T cell differentiation (IRM6P.716)

Naive CD4+ T cells differentiate into either helper (Th) or regulatory (Treg) cells following encounter with antigen. T cell fate is in part determined by signaling strength where lower TCR and AKT/mTOR signaling favors Treg differentiation and higher TCR and AKT/mTOR signaling drives Th differentiation. AKT/mTOR signaling is regulated by PTEN, a phosphatase that is highly expressed in Tregs. We recently published a computational model that suggested a critical role for PTEN in T cell differentiation. Our current work focuses on validating the model predictions and explaining how PTEN is regulated during T cell differentiation. We demonstrate that PTEN inhibition increases Akt/mTOR signaling leading to increased Th induction. When the TCR signal strength is high, PTEN is ubiquitinated and phosphorylated and PTEN protein levels are dramatically reduced. Conversely, PTEN levels only decrease transiently when TCR signal strength is low and the resulting Treg express higher PTEN levels. We are exploring the transcriptional regulation of PTEN. One potential regulator is FOXO1, which has been shown by ChIP-Seq to bind the PTEN promoter. High Akt/mTOR signaling results in phosphorylation of FOXO1 and exclusion of FOXO1 from the nucleus. Low Akt/mTOR signaling results in minimal phosphorylation and sustained FOXO1 nuclear localization. Thus, PTEN protein levels are tightly controlled by TCR signal strength and regulation of PTEN plays an important role in determining T cell fate.
Reactions of native proteins with chemical reagents.

Publisher Summary This chapter considers those chemical reactions that can be used to modify native proteins under such mild conditions that little or no denaturation may be expected. It is of considerable importance that no denaturation takes place, for if denaturation assumes appreciable proportions the system is very complicated and no reliable interpretation can be made of the results. Very few workers have established the fact that a chemical reaction has been carried through involving specific groups of a protein without denaturing the protein in the process. A few instances have been discussed in the present chapter in which denaturation undoubtedly accompanied the chemical reaction under examination. A correlation of the number of specific protein groups modified with the number of reagent residues introduced into the protein is another desirable feature of any study of the type covered by this chapter. In the case of oxidation or reduction reactions in which no reagent residues are attached to the protein the stoichiometry of the reaction provides equivalent information.
High and Higher Sensitivity CRP

The article by Roberts et al. (1) provided interesting data on automated methods for C-reactive protein (CRP) determinations. …
Relationship between a pulmonary function test (FEV1) and the ADAPT quality-of-life scale.

In a previous study the Additive Daily Activities Profile Test (ADAPT) correlated .83 with maximum oxygen consumption among pulmonary rehabilitation patients. The present study expanded the pulmonary population base and compared the ADAPT scores of 41 patients at two independent centers with a more readily available parameter, the forced expiratory volume in the first second of forced exhalation (FEV1). The relationships between the two major ADAPT subscales and FEV1 were significant but lower in magnitude than that found with maximum oxygen consumption. The ADAPT continues to be sensitive to physical impairment and in translating the effect of impairment upon daily physical activity.
Rhinovirus 16 3C protease induces interleukin-8 and granulocyte-macrophage colony-stimulating factor expression in human bronchial epithelial cells.

Rhinovirus (RV), a member of the Picornaviridae family, accounts for many virus-induced asthma exacerbations. RV induces airway cell chemokine expression both in vivo and in vitro. Because of the known interactions of proteases with cellular functions, we hypothesized that RV 3C protease is sufficient for cytokine up-regulation. A cDNA encoding RV16 3C protease was constructed by PCR amplification and transfected into 16HBE14o− human bronchial epithelial cells. 3C protease induced expression of both IL-8 and GM-CSF, as well as transcription from both the IL-8 and GM-CSF promoters. 3C expression also induced activator protein 1 and NF-κB transcriptional activation. Finally, mutation of IL-8 promoter AP-1 and NF-κB promoter sequences significantly reduced 3C-induced responses. Together, these data suggest expression of RV16 3C protease is sufficient to induce chemokine expression in human bronchial epithelial cells, and does so in an AP-1- and NF-κB–dependent manner.
Diazoxide and cyclothiazide convert AMPA-induced dark cell degeneration of Purkinje cells to edematous damage in the cerebellar slice

Using the in vitro cerebellar slice preparation from young rats (8-12 days old), AMPA produced in addition to dark cell degeneration (DCD), an edematous type of toxicity (edematous damage; ED) in a minority (35%) of Purkinje cells. The intent of this study was to evaluate whether AMPA receptor desensitization is a primary factor that governs the type of toxicity induced by AMPA in the in vitro cerebellar slice preparation. Both the competitive and noncompetitive AMPA antagonists CNQX and GYKI 52466, respectively, blocked ED when given during the entire protocol (30 min AMPA exposure followed by 90 min of recovery). Cyclothiazide (100 microM) and diazoxide (500 microM), two antagonists of AMPA receptor desensitization reversed DCD and unveiled a fulminating ED. Lowering Na+ and lowering Cl- proved effective in blocking ED, whereas removal of Ca2+ proved to be ineffective. Kainate (KA) (30-100 microM) produced only 50% as much ED as AMPA. This study indicates that AMPA can elicit more than one type of degeneration in the same neuronal population and that a primary governing factor in determining which toxicity is expressed seems to be the ability of AMPA receptors to desensitize.
Pentylenetetrazol may discriminate between different types of benzodiazepine receptors.

: The effect of various concentrations of pentylenetetrazol (PTZ) on [3H]flunitrazepam binding to benzodiazepine receptors was investigated by Hofstee and Hill plot analyses. These analyses indicate the presence of two PTZ binding sites in forebrain, whereas a single PTZ binding site is present in cerebellum. The relative proportions of the two PTZ binding sites in forebrain are close to those of benzodiazepine Type II and Type I receptors, respectively. These results suggest that PTZ may actually discriminate between different types of benzodiazepine receptors.
Genetic analysis of glucosinolate variability in broccoli florets using genome-anchored single nucleotide polymorphisms

The identification of genetic factors influencing the accumulation of individual glucosinolates in broccoli florets provides novel insight into the regulation of glucosinolate levels in Brassica vegetables and will accelerate the development of vegetables with glucosinolate profiles tailored to promote human health. Quantitative trait loci analysis of glucosinolate (GSL) variability was conducted with a B. oleracea (broccoli) mapping population, saturated with single nucleotide polymorphism markers from a high-density array designed for rapeseed (Brassica napus). In 4 years of analysis, 14 QTLs were associated with the accumulation of aliphatic, indolic, or aromatic GSLs in floret tissue. The accumulation of 3-carbon aliphatic GSLs (2-propenyl and 3-methylsulfinylpropyl) was primarily associated with a single QTL on C05, but common regulation of 4-carbon aliphatic GSLs was not observed. A single locus on C09, associated with up to 40 % of the phenotypic variability of 2-hydroxy-3-butenyl GSL over multiple years, was not associated with the variability of precursor compounds. Similarly, QTLs on C02, C04, and C09 were associated with 4-methylsulfinylbutyl GSL concentration over multiple years but were not significantly associated with downstream compounds. Genome-specific SNP markers were used to identify candidate genes that co-localized to marker intervals and previously sequenced Brassica oleracea BAC clones containing known GSL genes (GSL-ALK, GSL-PRO, and GSL-ELONG) were aligned to the genomic sequence, providing support that at least three of our 14 QTLs likely correspond to previously identified GSL loci. The results demonstrate that previously identified loci do not fully explain GSL variation in broccoli. The identification of additional genetic factors influencing the accumulation of GSL in broccoli florets provides novel insight into the regulation of GSL levels in Brassicaceae and will accelerate development of vegetables with modified or enhanced GSL profiles.
The inhibitory effects of anticoagulation on in vivo gene transfer by adeno-associated viral or adenoviral vectors

Identifying factors that influence gene transfer efficacy is critical for a successful gene-based clinical study. Here we demonstrate that in vivo AAV-2-mediated gene transfer is efficiently inhibited by unfractionated heparin, but not by a heparin preparation containing mainly low-molecular-weight forms (LMWH). Surprisingly, inhibitors of thrombin or factor Xa (F.Xa) significantly reduced AAV-2 transduction in a dose-dependent manner. These effects were independent of the vector promoter, transgene, or strain of mice. Expression by alternate AAV serotypes 5 and 8 was not affected by anticoagulant drugs, which suggests an AAV-2-specific effect. Moreover, AAV-2-mediated gene expression was diminished in mice with deficiency in thrombin generation (factor IX deficiency) and enhanced in mice with procoagulant phenotype due to factor V Leiden. In addition, inhibitors of F.Xa diminished adenovirus-mediated gene expression. These results demonstrated that coagulation activity itself is critical to ensure optimal viral vector transduction. Since intravascular delivery of vectors often requires the use of anticoagulants, the use of LMWH appears to be safe. These observations are of relevance for approaches using AAV-2 or adenoviral vectors, especially in early phase studies designed to identify the minimum therapeutic doses.
Gray Matter: Daniel Arsham, Jonah Bokaer, and Judith Sánchez Ruíz's REPLICA

In REPLICA, Daniel Arsham, Jonah Bokaer, and Judith Sanchez Ruiz attempt to replicate the capacities of the human brain through movement, highlighting the intertwined layers of perception and memory.
Older age predicts a decline in adjuvant chemotherapy recommendations for patients with breast carcinoma: evidence from a tertiary care cohort of chemotherapy-eligible patients.

BACKGROUND The appropriate use of adjuvant chemotherapy for elderly women with breast carcinoma remains controversial. Efficacy data in women age ≥ 70 years are scarce, resulting in a lack of clear guidelines for patients in this age group. Although several studies have demonstrated decreasing use of chemotherapy with age, none specifically examined its use in an elderly cohort of patients who were deemed eligible for such therapy based on consensus guidelines, simultaneously examining the impact of comorbidity and previous history of malignant disease on these recommendations. METHODS The authors examined adjuvant chemotherapy use among chemotherapy-eligible patients age ≥ 50 years who were evaluated in a tertiary care cancer center. Associations between patient age and 1) physician recommendation for adjuvant chemotherapy, 2) recommended treatment regimen, and 3) patient acceptance of the treatment plan recommended were examined, adjusting for the impact of aggressive tumor characteristics, medical comorbidity, previous history of malignant disease, and features of the treatment setting. RESULTS Of the 208 chemotherapy-eligible patients who were studied, 74% overall were recommended chemotherapy. Chemotherapy was recommended to 92% of women age 50–59 years compared with 77% of women age 60–69 years and 23% of women age ≥ 70 years. Increasing age was associated strongly with a decreasing likelihood of receiving a recommendation in favor of chemotherapy. After adjusting for estrogen receptor status, previous history of malignant disease, comorbidity score, and prognostic group, the odds of receiving a recommendation in favor of chemotherapy fell by 22% per year or 91% per 10-year interval, and the rate of decline did not change significantly at age ≥ 70 years. We found no age-related differences in either the drug regimens recommended or patient acceptance rates for adjuvant therapy. CONCLUSIONS Age was associated strongly and independently with physician recommendation for adjuvant chemotherapy among a group of older women who were eligible specifically for such therapy. Medical comorbidity and a history of previous malignant disease did not alter this correlation significantly, although the latter was a significant predictor of chemotherapy use. Further studies clearly are needed to determine the underlying reasons for this strong age effect and to explore strategies that will optimize the utilization of this potentially curative therapy in the elderly. Cancer 2003;97:2150–9. © 2003 American Cancer Society. DOI 10.1002/cncr.11338
Caring for the chronically ill: a vital subject for medical education.

The growing prevalence of chronic illness will be the predominant challenge to the American health care system in the coming century. Patients with chronic conditions account for three fourths of U.S. health care expenditures, and considerable growth of these costs is likely as the population ages. Despite the enormity of this problem, the management of chronic illness has received little attention in undergraduate and graduate medical education. This paper describes the competencies required to develop curricula in the management of chronic illness.
Partial purification and characterization of the antidiuretic hormone-inactivating enzyme from renal plasma membranes

Abstract An antidiuretic hormone-inactivating peptidase located in renal plasma membranes of porcine kidney medulla has been studied. Treatment of antidiuretic hormone (lysine vasopressin) with renal plasma membranes resulted in a progressive loss of biological activity as measured by the rat pressor assay. The reaction of 2,4,6-trinitrobenzenesulfonic acid with released amino groups was employed to follow the peptidase-catalyzed hydrolysis of the hormone. An 83-fold purification of the membrane-bound peptidase was achieved by Lubrol PX solubilization of the membranes followed by DEAE-cellulose, hydroxylapatite, and 8% agarose column chromatography. The molecular weight of the peptidase was 442 000 as determined by 8% agarose gel filtration. An analysis of the antidiuretic hormone hydrolysis products by thin-layer chromatography revealed the presence of trinitrophenyl-glycinamide. The release of glycinamide from the hormone as a function of time was demonstrated. Mg2+ had a slight inhibitory effect and Ca2+ had a strong inhibitory effect on the peptidase activity.
Complaints of Everyday Life: Feminist Periodical Culture and Correspondence Columns in The Woman Worker, Women Folk and The Freewoman

This chapter explores the ephemeral aspects of everyday life through marginal forms of periodical culture—the lively correspondence columns of two very different feminist papers, the avant-garde little magazine, the Freewoman, and the socialist woman's paper, the Woman Worker. Letters columns reveal the traces of readers’ interactions with a paper and highlight the ways in which feminist periodicals addressed their readers, invited them to try on new identities, and engaged them in the debates of the public sphere. Using Lauren Berlant's description of a “female complaint” of modern mass cultural forms, this chapter unpacks the ways in which the letters that aired female discontent with the everyday open a new view onto the feminist readings of daily life offered by feminist print.
Electrowetting-Induced Droplet Movement in an Immiscible Medium

This paper describes and characterizes the electrowetting-induced movement of droplets in an immiscible medium. When an aqueous droplet undergoes electrowetting-induced motion in a continuous phase of olive oil, the droplet glides through the olive oil at a much higher velocity than is possible in the absence of oil and is able to travel greater than 10 times the electrode separation distance. To describe this behavior, a simple hydrodynamic model is developed to predict the droplet speed and to elucidate the mechanism of droplet movement. On the basis of this model, we also discuss a strategy to reduce droplet splitting.
Experimental pancreatic fistula; a simple and satisfactory method for investigating the external function of the pancreas

It is perhaps trite but a truism to say that advances in physiology depend to a considerable extent upon improvements in technical methods. Much of the data of classical physiology has of necessity been derived from acute mammalian experiments. The value of experimental data obtained from investigation of intact, unanesthetized animal preparations is self evident. In this respect study of external function of the pancreas is greatly favored by the use of total permanent external pancreatic fistula animals, in which unphysiologic factors are largely eliminated. The technic of fistula preparation described here (retrograde external pancreatic fistula) affords simplicity of technic with low immediate operative mortality and a high percentage of successful results. There is a minimum chance for pancreatic infection, and no interference with nerve supply and only a negligible interference with blood supply. No apparent atrophy of the pancreas was observed grossly or microscopically after four months.
Spatial Variability of Sea Level Rise in Twenty-First Century Projections

Abstract A set of state-of-the-science climate models are used to investigate global sea level rise (SLR) patterns induced by ocean dynamics in twenty-first-century climate projections. The identified robust features include bipolar and bihemisphere seesaws in the basin-wide SLR, dipole patterns in the North Atlantic and North Pacific, and a beltlike pattern in the Southern Ocean. The physical and dynamical mechanisms that cause these patterns are investigated in detail using version 2.1 of the Geophysical Fluid Dynamics Laboratory (GFDL) Coupled Model (CM2.1). Under the Intergovernmental Panel on Climate Change’s (IPCC) Special Report on Emissions Scenarios (SRES) A1B scenario, the steric sea level changes relative to the global mean (the local part) in different ocean basins are attributed to differential heating and salinity changes of various ocean layers and associated physical processes. As a result of these changes, water tends to move from the ocean interior to continental shelves. In the North At...
Bacterial ureases: structure, regulation of expression and role in pathogenesis

The nickel metalloenzyme urease catalyses the hydrolysis of urea to ammonia and carbamate, and thus generates the preferred nitrogen source of many organisms. When produced by bacterial pathogens in either the urinary tract or the gastroduodenal region, urease acts as a virulence factor. At both sites of infection urease is known to enhance the survival of the infecting bacteria. Ammonia resulting from the action of urease is believed to increase the pH of the environment to one more favourable for growth, and to injure the surrounding epithelial cells. In addition, in the urinary tract urease activity can result in the formation of urinary calculi. Bacterial urease gene clusters contain from seven to nine genes depending upon the species. These genes encode the urease structural subunits and accessory polypeptides involved in the biosynthesis of the nickel metallocentre. So far, three distinct mechanisms of urease gene expression have been described for ureolytic bacteria. Some species constitutively produce urease; some species produce urease only if urea is present in the growth medium; and some species produce urease only during nitrogen-limiting growth conditions. For either the urea-inducible genes or the nitrogen-regulated genes transcription appears to be positively regulated. In the nitrogen-regulated systems, urease gene expression requires Nac (nitrogen assimilation control), a member of the LysR family of transcriptional activators. Urea dependent expression of urease requires UreR (urease regulator), a member of the AraC family of transcriptional activators. An evolutionary tree for urease genes of eight bacterial species is proposed.
Phase transition and abnormal compressibility of lanthanide silicate with the apatite structure

The lanthanide silicate La${}_{9.33}$Si${}_{6}$O${}_{26}$, which has the hexagonal apatite structure ($P{6}_{3}$/$m$), was investigated at high pressure. A subtle phase transition was observed at \ensuremath{\sim}13.3 GPa by in situ synchrotron x-ray diffraction and confirmed by infrared absorption and Raman scattering measurements. The high-pressure phase has a structure similar to that of the initial hexagonal apatite structure, but the symmetry is reduced to $P{6}_{3}$ through the displacement of one oxygen site and tilting of the SiO${}_{4}$ tetrahedra. Interestingly, the high-pressure phase has an abnormally lower compressibility, which is caused by the change in symmetry that allows the tilting of the SiO${}_{4}$ tetrahedra, and the bulk modulus of the high-pressure phase is only half that of the apatite structure.
Blunt cerebrovascular injuries

On the basis of our experience and the available literature, we submit that aggressive screening for BCI based on injury patterns is warranted. However, several important clinical issues remain unresolved. The precise injury patterns and relative cerebrovascular risks remain to be defined. Furthermore, the optimal diagnostic screening test remains to be identified, with consideration of the relative risk-benefit profile. Finally, we must determine the best methods for the treatment of BCI. Although the definitive study has yet to be completed, the use of heparin was associated with a trend toward improved outcomes in symptomatic patients. In addition, no asymptomatic patient experienced the development of new neurologic deficits during heparin therapy. Therefore we believe that the early institution of heparin therapy is indicated. The role of endovascular stenting, however, remains unclear.
Aphidicolin hypersensitive mutant of chinese hamster V79 fibroblasts that underproduces DNA polymerase-α antigen

Aphidicolin is a specific inhibitor of DNA polymerase-α and -δ from eukaryotic cells. Because of the specificity of this inhibitor, it is potentially a useful probe for the detailed studies of the function of these polymerases. DNA polymerase-α mutants isolated on the basis of resistance to aphidicolin have been described. We have isolated four variants that exhibit hypersensitivities to aphidicolin (Aphhs) from Chinese hamster V79/743X fibroblasts. These variants are designated aphhs-1, aphhs-2, aphhs-3 and aphhs-4. We reported here results of studies involving immunochemical characterization. The Aphhs phenotype in all mutants was stable for at least 30 days in the absence of selection pressure. The dCTP pools in the 743X and Aphhs cell lines were not significantly different. The level of total DNA polymerase activity in the crude extract from aphhs-2 cells was 30% of that observed in the parental 743X clone. We developed a method to quantitate DNA polymerase-α antigen at single cells in situ using monoclonal antibody SJK 132-20 and fluorescence pseudocolor image. We found that the antigen of DNA polymerase-α in aphhs-2 was 30–50% of that in the parental 743X cells. The underproduction of the antigen of DNA polymerase-α provides a basis for the observed Aphhs phenotype. Possible mechanisms for the underproduction of DNA polymerase-α in aphhs-2 clone are presented.
CLEAVAGE EN BLOC OF N-ACETYLGLUCOSAMINE-6-SULFATE AND N-ACETYLGALACTOSAMINE-6-SULFATE BY HEXOSAMINIDASE A: DEFICIENCY OF BOTH ACTIVITIES IN TAY-SACHS DISEASE

Current assays of hexosaminidase A (Hex A) are either indirect (heat-inactivation method) or complex (GM2 ganglioside substrate). The finding in Sanfilippo syndrome type D (N-acetylglucosamine-6-sulfatase deficiency) that Hex A can bypass the blockage in keratan sulfate degradation by cleavage en bloc of β-N-acetyl-glucosamine-6-sulfate, led to the present approach. 4-methyl-umbelliferyl derivatives of β-N-acetylglucosamine-6-sulfate (MUβG1cNAc-6-S) and β-N-acetylgalactosamine-6-sulfate (MUβGa1NAc-6-S) were prepared from the commonly used unsulfated derivatives. Sera (n=5), leukocytes (n=3) and fibroblasts (n=2) from patients with Tay-Sachs disease (TSD) demonstrated markedly deficient activities toward both sulfated substrates, 2-4% of control activities (n=12), and samples from obligate heterozygotes for TSD (n=4) had intermediate activity values, 43-62% of control activities. Fibroblasts (n=2) from patients with Morquio syndrome type A (N-acetylgalactosamine-6-sulfatase deficiency) had normal activities toward both sulfated substrates but the characteristic urinary excretion of chondroitin sulfate in this disease, indicates that there is no analogy with Sanfilippo syndrome type D and Hex A is incapable of cleaving en bloc βGa1NAc-6-S from the natural substrate. In contrast to natural substrates, the synthetic sulfated substrates are both specific for Hex A and thus, can provide direct and simple methods for diagnosis as well as for antenatal and carrier detection of TSD.
Chronic exercise dampens hippocampal glutamate overflow induced by kainic acid in rats

Our laboratory has previously reported that chronic, voluntary exercise diminishes seizure-related behaviors induced by convulsant doses of kainic acid. The present experiments tested the hypothesis that exercise exerts this protective effect through a mechanism involving suppression of glutamate release in the hippocampal formation. Following three weeks of voluntary wheel running or sedentary conditions, rats were injected with 10 mg/kg of kainic acid, and hippocampal glutamate was measured in real time using a telemetric, in vivo voltammetry system. A separate experiment measured electroencephalographic (EEG) activity following kainic acid treatment. Results of the voltammetry experiment revealed that the rise in hippocampal glutamate induced by kainic acid is attenuated in exercising rats compared to sedentary controls, indicating that the exercise-induced protection against seizures involves regulation of hippocampal glutamate release. The findings reveal the potential benefit of regular exercise in the treatment and prevention of seizure disorders and suggest a possible neurobiological mechanism underlying this effect.
Clinical applications of epigenetics in cardiovascular disease: the long road ahead

Epigenetic processes, defined as heritable changes in gene expression that occur without changes to the DNA sequence, have emerged as a promising area of cardiovascular disease research. Epigenetic information transcends that of the genotype alone and provides for an integrated etiologic picture of cardiovascular disease pathogenesis because of the interaction of the epigenome with the environment. Epigenetic biomarkers, which include DNA methylation, histone modifications, and RNA-based mechanisms, are both modifiable and cell-type specific, which makes them not only responsive to the environment, but also an attractive target for drug development. However, the enthusiasm surrounding possible applications of cardiovascular epigenetics currently outpaces available evidence. In this review, the authors synthesize the evidence linking epigenetic changes with cardiovascular disease, emphasizing the gap between the translational potential and the clinical reality of cardiovascular epigenetics.
Photoionization of fluoranthene in dielectric liquids

Abstract The effect of electron attaching additives on the photoionization threshold of fluoranthene in dielectric liquids has been studied. The results show that solvation of the positive-negative ion pair plays a key role in the energetics of the photoionization process.
Salvage Therapy with High-Dose Chemotherapy and Peripheral Blood Stem Cell Transplant in Patients with Primary Mediastinal Nonseminomatous Germ Cell Tumors

Salvage therapy with high-dose chemotherapy (HDCT) and bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) has curative potential in patients with recurrent germ cell tumor. However, patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs) have had poor results with any form of salvage chemotherapy including HDCT. We switched from BMT to PBSCT in 1996. One hundred sixteen of 184 patients (63%) with recurrent or refractory germ cell tumors treated from 1996 to 2004 were alive and continuously disease-free. PMNSGCTs were excluded from that study because of poor results in the patient population with HDCT and BMTs. In 2006, we resumed treating patients with recurrent PMNSGCT with 2 consecutive courses of HDCT consisting of carboplatin 700 mg/m(2) × 3 plus etoposide 750 mg/m(2) × 3 and each followed by an infusion of autologous peripheral-blood hematopoietic stem cells with a second course 3 to 4 weeks later. Twelve patients were treated: 11 as initial salvage chemotherapy and 1 as fourth-line therapy. Eight of the 12 patients had major thoracic resections at the time of the relapse after initial chemotherapy. Three of the 12 patients achieved complete remission (CR; 10, 15, and 50 months' duration). One patient remains continuously with no evidence of disease (NED) at 50 months. An additional patient is currently NED at 52 months with HDCT and subsequent surgery. Median survival for the 12 patients was 11 months (range, 4-52 months). Results with tandem transplant for recurrent PMNSGCT remain poor compared to primary testis cancer, but durable CR and probable cure can be achieved in a small subset of patients with PMNSGCT. In our opinion, salvage surgical resection if anatomically feasible is the preferred option for patients with PMNSGT progressing after initial chemotherapy.
Sea Level and the Seasonal Fluctuations of the Equatorial Currents in the Western Pacific Ocean

Abstract The seasonal variations of the dynamic topography relative to 500 decibars in the western equatorial Pacific, using data from 6900 hydrographic stations, are compared with the seasonal fluctuations of sea level observed at eleven islands. It is shown that the changes in the meridional profile of sea level correlate with changes in the strength of the major ocean currents measured by their speed or by geostrophic transports. The strength of the North Equatorial Current and that of the Countercurrent vary synchronously, both being strong in fall and weak in spring. The South Equatorial Current varies exactly out of phase with the two Northern Hemisphere currents, but is apparently in phase with the Undercurrent. Investigation of the particular example indicates that large anomalies seem to behave in the same fashion as the seasonal fluctuations of these currents.
The Politics of the Death Penalty

What seemed unimaginable a decade ago, namely, the abolition of the death penalty in the United States, today seems well within the horizon of possibility. Indeed, supporters of capital punishment now seem to be very much on the defensive. To take but one example, in April 2005, then Massachusetts Governor Mitt Romney filed a long-awaited bill to reinstate the death penalty in his state. The bill, which Romney called “a model for the nation” and the “gold standard” for capital punishment legislation, was remarkable for its hesitations and qualifications. Thus, it limited death eligibility to a narrow set of crimes, including deadly acts of terrorism, killing sprees, murders involving torture, and the killing of law enforcement authorities. It excluded entire categories of crimes that many believe also warrant the death penalty, including the murders of children and the rape-murders of women. It also laid out a set of hurdles for meting out capital punishment sentences, in an effort to neutralize the kind of problems that have led to dozens of death row exonerations across the nation in recent years. The measure called for verifiable scientific evidence, such as DNA, to be required before a defendant can be sentenced to death, and a tougher standard of “no doubt” of guilt (rather than the typical “guilty beyond a reasonable doubt” standard) for juries to sentence defendants to death. The limited nature of Romney's bill, which nonetheless ultimately was defeated in the Massachusetts legislature, provides one vivid sign that the tide has turned in the national conversation about capital punishment.
Cysteinyl leukotriene expression in chronic hyperplastic sinusitis–nasal polyposis: Importance to eosinophilia and asthma

Abstract Background: Chronic hyperplastic eosinophilic sinusitis (CHS) results from the unregulated proliferation of eosinophils, T H 2-like lymphocytes, goblet cells, mast cells, and fibroblasts and is present in most patients with asthma. The frequent coexpression of these disorders and their shared pathophysiology suggests that these are similar disorders affecting the upper and lower airways. Objective: We evaluated the expression of cysteinyl leukotrienes (CysLTs) in sinus tissue from subjects with CHS compared with that seen in healthy sinus tissue. Methods: Nasal polyp and sinus tissue was evaluated from 58 individuals undergoing elective functional endoscopic sinus surgery. The diagnosis of CHS was demonstrated through the presence of eosinophilia and activated (EG2 + ) eosinophils, as determined by means of tissue immunohistochemistry. Data were compared with those from both nasal polyp tissue without eosinophilic inflammation and healthy control sinus tissue obtained from the sinus ostiomeatal complex at the time of surgery for unrelated disorders. CysLTs were quantified by means of ELISA in lipid-extracted tissue. Activation of the metabolic pathway leading to CysLT synthesis was demonstrated by ribonuclease protection. Subjects were genotyped for leukotriene C 4 (LTC 4 ) synthase C-to-A promoter polymorphism. Results: CysLT concentrations were significantly higher in tissue obtained from subjects with CHS (776.7 ± 201.9 pg/g tissue) compared with that seen in healthy sinus tissue (355.7 ± 101.6 pg/g tissue, P 4 synthase mRNA. The C-to-A promoter polymorphism was associated with trends toward the increased presence of CHS and CysLTs. Conclusions: CHS is characterized by the increased presence of CysLTs when compared with concentrations seen in tissue from patients with chronic inflammatory sinusitis or healthy sinus tissue. These studies support the use of LT modifiers as anti-inflammatory agents that might have clinical benefit in patients with these disorders. (J Allergy Clin Immunol 2003;111:342-9.)
Evaluation of Longissimus dorsi muscle pH at three hours Post mortem as a predictor of beef tenderness.

Abstract The objective of this study was to determine the relationship of beef longissimus dorsi muscle (LM) pH at 3 h post mortem (pH 3 ) and aged LM tenderness. The cattle ( n = 444) sampled for this experiment represented various breed types, sex classes, feeding regimes, and post-mortem handling practices. The phenotypic diversity of the cattle used provided a great amount of variation in Warner-Bratzler shear (WBS) force (Coefficient of variation for pH, temperature, and sarcomere length measurements were much smaller than the coefficient of variation for WBS force). None of the parameters measured (LM pH at 3 and 48 h post mortem , temperature at 3 h post mortem and sarcomere length) was strongly related to tenderness. These results do not support the use of pH 3 as a criterion for sorting beef carcasses into expected tenderness groups.
Using the BIDR to Distinguish the Effects of Impression Management and Self‐Deception on the Criterion Validity of Personality Measures: A Meta‐Analysis

Although the use of personality tests for personnel selection has gained increasing acceptance, researchers have raised concerns that job applicants may distort their responses to inflate their scores. In the present meta-analysis, we examined the effects of the two dimensions of social desirability, impression management and self-deception, on the criterion validity of personality constructs using the balanced inventory of desirable responding (BIDR). The results indicate that impression management and self-deception did not create spurious effects on the relationship between personality measures and performance, nor did they function as performance predictors. Moreover, removing the influence of impression management or self-deception from personality measures did not substantially attenuate the criterion validity of personality variables. Implications of the results and directions for future research are also discussed.
Resource curse: the role of institutions versus policies

Recent work suggests that countries with good institutions can escape the resource curse. This article shows that in the developing countries where the curse is of primary concern, institutional quality does not seem to have much influence; instead, it appears that it is a country's policies which play a significant role in neutralizing the negative impact of resource abundance.
Preparation of heparin-linked agarose and its interaction with plasma.

Abstract Heparin was linked covalently to Agarose by a reaction between aminoethyl Agarose and heparin in the presence of a water-soluble carbodiimide. Treatment of plasma with this product resulted in prolongation of coagulation and partial thromboplastin times. Assays of the treated plasma revealed that it was deficient in factors IX and XI. Elution of the heparin-linked Agarose with salt solutions yielded fractions containing these factors. Similar studies with serum indicated that heparin-cofactor is also bound to the immobilized heparin.
Surgical management of the adrenal glands in the multiple endocrine neoplasia type II syndrome.

During a 30-year period (1951–1981), seventeen patients underwent bilateral adrenalectomy for established adrenal medullary disease with catecholamine excess. Fourteen patients had the MEN IIa syndrome and 3 had the MEN IIb syndrome. There was no major operative morbidity and no operative mortality. One patient died 23 months after initial operation because of metastatic pheochromocytoma. The remaining patients were followed for a mean of 129 months and all were personally interviewed. Three patients had 7 uneventful pregnancies. Twelve patients underwent 23 other surgical procedures requiring general anesthesia during the followup period without any morbidity. Two patients have metastatic pheochromocytoma; 3 have clinical metastatic medullary thyroid carcinoma; 5 patients have high calcitonin values and 6 patients are in excellent health at intervals of 15, 27, 58, 110, 134, and 373 months following resection. The need for adrenal replacement therapy has not caused significant problems in any patient. The results of this study confirm that bilateral total adrenalectomy is a safe modality for the treatment of adrenal medullary disease in this syndrome and that it does not produce significant long-term morbidity.
Effective plague vaccination via oral delivery of plant cells expressing F1-V antigens in chloroplasts.

The chloroplast bioreactor is an alternative to fermentation-based systems for production of vaccine antigens and biopharmaceuticals. We report here expression of the plague F1-V fusion antigen in chloroplasts. Site-specific transgene integration and homoplasmy were confirmed by PCR and Southern blotting. Mature leaves showed the highest level of transgene expression on the third day of continuous illumination, with a maximum level of 14.8% of the total soluble protein. Swiss Webster mice were primed with adjuvant-containing subcutaneous (s.c.) doses of F1-V and then boosted with either adjuvanted s.c. doses (s.c. F1-V mice) or unadjuvanted oral doses (oral F1-V mice). Oral F1-V mice had higher prechallenge serum immunoglobulin G1 (IgG1) titers than s.c. F1-V mice. The corresponding serum levels of antigen-specific IgG2a and IgA were 2 and 3 orders of magnitude lower, respectively. After vaccination, mice were exposed to an inhaled dose of 1.02 × 106 CFU of aerosolized Yersinia pestis CO92 (50% lethal dose, 6.8 × 104 CFU). All control animals died within 3 days. F1-V given s.c. (with adjuvant) protected 33% of the immunized mice, while 88% of the oral F1-V mice survived aerosolized Y. pestis challenge. A comparison of splenic Y. pestis CFU counts showed that there was a 7- to 10-log reduction in the mean bacterial burden in survivors. Taken together, these data indicate that oral booster doses effectively elicit protective immune responses in vivo. In addition, this is the first report of a plant-derived oral vaccine that protected animals from live Y. pestis challenge, bringing the likelihood of lower-cost vaccines closer to reality.