cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 2557: Preclinical synergy of Plk1 inhibitors and HDACIs

Our laboratory is interested in the synergy between spindle check point inhibitors and histone deacetylase inhibitors (HDACIs). Previous work investigated two polo-like kinase inhibitors in prostate cancer and in non-small cell lung cancer (NSCLC). In preliminary studies we have investigated two polo-like kinase inhibitors, BI2536 and BI6727, in NSCLC cell lines H358 and H1838. In MTS proliferation assays, we found a significant inhibition of proliferation (For H358 the IC50 = 100nM for BI2536and BI672; and for H1838 the IC50 = 25nM for BI2536 and 50nM for BI6727). In clonogenic assays both polo-like kinase inhibitors caused a dose dependent inhibition of proliferation and survival in NSCLC. We explored these findings further with western blot analysis and found that both compounds arrested both cell lines in G2/M transition with elevated phosphorylated histone H3 and elevated cyclin B1. These findings show that polo-like kinase can be effectively targeted in NSCLC by these compounds. Given other studies in lung and prostate demonstrating down regulation of mitotic spindle proteins upon treatment with HDACIs, we plan to combine polo-like kinase inhibitors and HDACIs to investigate for additive or synergistic effects in NSCLC cell lines as has been seen in prostate cancer cell lines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2557. doi:10.1158/1538-7445.AM2011-2557
Insights into the Holley- and Joseph- phenotypes.

Background The Dombrock blood group system consists of two antithetical antigens (Do(a) and Do(b)) and three high-incidence antigens (Gregory [Gy(a)], Holley [Hy], and Joseph [Jo(a)]). Hy and Jo(a) have an unusual phenotypic relationship. All Hy- RBCs are Jo(a-), but not all Jo(a-) RBCs are Hy-. The molecular background associated with Hy- and Jo(a-) phenotypes is reported. Study design and methods DNA from 18 probands with Gy(a+(w)) Hy- Jo(a-) RBCs (Hy- phenotype) and from 13 probands with Gy(a+) Hy+(w) Jo(a-) RBCs (Jo[a-] phenotype) was tested. Results Sequencing and PCR-RFLP revealed 323 G>T (Gly 108Val) and 378 T>C (silent mutation) changes on a DOB background (HY) associated with the Hy- samples. The sister of the original Hy- proband and the majority of samples had an additional mutation of 898 C>G (Leu300Val) (HY1); others had 898C (300Leu) (HY2). In the Jo(a-) phenotype, there is a 350 C>T (Thr1 17Ile) and a 378 C>T (silent mutation) change on a DOA background (JO). Conclusion The results provide an explanation for the variation in typing results in antibody producers. The ablation of Jo(a) in the Hy- phenotype and the weakening of Hy in the Jo(a-) phenotype may be due to the close proximity of these antigens. The 898 C>G mutation, within the sequence motif for glycosylphosphatidylinositol linkage, may cause reduced efficiency of anchoring the protein to the RBC membrane, thereby weakening the expression of Gy(a) and Do(b).
Perineal talc exposure and subsequent epithelial ovarian cancer: a case-control study.

Abstract Objective: To evaluate the role of talcum powder use as a risk factor for the development of epithelial ovarian cancer. Methods: In a case-control study, 499 patients with epithelial ovarian cancer were frequency matched for age at diagnosis (±5 years) with a control population of 755 patients. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, education, geographic location, history of tubal ligation, and previous hysterectomy. Results: Two hundred twenty-one of 462 patients (47.8%) in the study population and 311 of 693 patients (44.9%) in the control population had ever used talcum powder (OR 0.92; 95% confidence interval [CI] 0.24, 3.62). A significant association between duration of talc use and development of epithelial ovarian cancer was not demonstrable for 1–9 years (OR 0.9; 95% CI 0.6, 1.5), for 10–19 years (OR 1.4; 95% CI 0.9, 2.2), or for more than 20 years (OR 0.9; 95% CI 0.6, 1.2). To eliminate the possible confounding variable of surgery for the management of ovarian cancer, we omitted 135 patients in the study population who underwent hysterectomy within 5 years of the diagnosis of ovarian cancer. Within this subgroup of patients, tubal ligation or hysterectomy among talc users still failed to demonstrate an increased risk for the development of ovarian cancer (OR 0.9; 95% CI 0.4, 2.2). Conclusion: A significant association between the use of talcum powder and the risk of developing epithelial ovarian cancer is not demonstrable, even with prolonged exposure.
Effect of thermal stress on cell proliferation of the submandibular gland and periodontal ligament of CH3-male mice

Abstract Eight experimental mice heated to 42 ± 0.2 °C (rectal temperature) received a pulse dose of [3H]-thymidine 2 hr before sacrifice at intervals ranging from 2 to 96 hr after thermal treatment. Autoradiography of submandibular glands and periodontal ligaments from experimental and eight control (not heated) mice showed depression of initial labelling indices of experimental acinar cells and periodontal ligament fibroblasts. Subsequently, peak values were recorded at 4–8 hr (acinar cells) and 24–48 hr (fibroblasts). These were approximately double those recorded for control tissues. Thereafter experimental tissues showed a gradual return to normal labelling indices.
Evaluation of the RF field uniformity of a double-tuned 31P/1H birdcage RF coil for spin-echo MRI/MRS of the diabetic foot.

Purpose To evaluate the B1 field uniformity of a double-tuned birdcage coil designed for 31P/1H MRI/MRS spin-echo (SE) imaging of the metatarsal head region of the foot in neuropathic diabetic patients. Materials and Methods A low-pass double-tuned 31P/1H RF birdcage coil was constructed to fit over the adult forefoot. Flip angle (FA) maps were created from B1 data acquired at the 3T 31P (four normal subjects) and 1H (five normal subjects) frequencies. T2-weighted (T2-W) 1H images, 31P rapid acquisition with relaxation enhancement (RARE) images, and composite SE pulse CSI data were acquired to demonstrate the uniformity of the resulting images and data. Results The means and standard deviations (SDs) of the range of FAs across the feet of the volunteer subjects indicated good uniformity (the maximum coefficients of variation (CVs) for all of the 31P and 1H FA maps were 7.6% and 7.3%, respectively). The FA values across the metatarsal head region indicated a maximum signal intensity variation of ±3% in a RARE image acquired using an echo train length of 32. Conclusion A 31P/1H birdcage coil constructed for MRI/MRS studies of the human forefoot provided sufficient signal uniformity of SE data to facilitate accurate 31P concentration measurements in muscle. J. Magn. Reson. Imaging 2005. © 2005 Wiley-Liss, Inc.
Design of Parenteral Magnesium Load Tests in Weanling and Young Adult Rats

AbstractThere is great difficulty in assessing the nutritional status of magnesium (Mg) in young, living mammals. The parenteral Mg load test has been advocated as a useful indicator, but requires further study, first of all, in an animal model. The present study was conducted to (a) design an appropriate Mg load test for Mg-deficient and Mg-sufficient rats in two age groups—weanling and young adults, and (b) to learn whether or not the test can be effectively conducted by giving the parenteral load of Mg by the intramuscular (im) route instead of the intraperitoneal (ip) or intravenous (iv). To design the parenteral Mg load test, all animals were fed identical purified diets, except for the addition of 150 mg of magnesium/100 g of diet in the control diets and zero magnesium in the deficient diet which contained only 0.3 mg/100 g. Plasma and urinary Mg values were followed. The final test included: (a) a fasting 6-hr preload urinary collection, (b) an 18-hr refeeding period, (c) intraperitoneal loading w...
Presidential Succession in the United States

The attitude of Congress toward presidential succession resembles that of the farmer who never repaired his roof because during fair weather it was unnecessary and when it rained it was too late. Ordinarily presidential succession receives scant attention; but, when a Vice President takes over the office of President and there is no Vice President, concern over the question of succession in some instances approaches a state of panic. Voters select the President and Vice President but beyond this point it is necessary to vest the line of succession in officers of the United States who were not selected for this high office. It is probable, therefore, that no plan of succession will ever meet with the unanimous approval of Congress or of the people.1 The constitutional fathers realized that a definite line of succession was both necessary and desirable but did nothing about it except to pass the responsibility to Congress. In Article II, Section I of the Constitution, Congress is given power to declare, when there is neither a President nor a Vice President, "what officer shall then act as President, and such officer shall act accordingly until the disability is removed or a President shall be elected." The method of succession is thus left to Congress to determine. One very remarkable fact is that while Presidents and Vice Presidents have died in office, never has any other officer been called upon to fill the office of President. Presidents W. H. Harrison, Taylor, Lincoln, Garfield, McKinley, Harding, and F. D. Roosevelt died while holding office. The Vice Presidents who have died in office are George Clinton, Elbridge Gerry, William R. King, Henry Wilson,
The effects of cyclooxygenase‐2 inhibition on apoptosis and cell cycle distribution using two in vitro models of nasal squamous cell carcinoma

Objective: Despite numerous attempts using a variety of therapeutic modalities, response rates and survival times for canine nasal squamous cell carcinoma remain poor. The goals of this study are to determine if a COX-2 selective inhibitor induces apoptosis and alters cell cycle distribution in two in vitro models of nasal squamous cell carcinoma, and to establish a basis for future clinical trials using COX-2 inhibitors as radiosensitizing agents. Methods: The nasal squamous cell carcinoma cell lines FAT-7 (rat) and RPMI 2650 (human) were purchased from ATCC (Manassas, VA). Cell pellets were stained for COX-2 expression using standard immunohistochemical techniques. Following the determination of growth kinetics for each cell line, cells were plated in triplicate using 25 cm2 tissue culture flasks and incubated with different concentrations of a COX-2 selective inhibitor (0, 1, 10, 50 and 100 μM) for 72 hours. Cells were stained with Annexin-V and propidium iodide (Oncogene Research Products) and analyzed with flow cytometry to assess cell viability. Cell cycle distribution was determined using a propidium iodide methodology and flow cytometric analysis. Results: Preliminary results show that the addition of a COX-2 selective inhibitor caused a dose-dependent cytotoxicity on the FAT-7 cells. Viability at 72 hours ranged from 95.4% for control samples to 7.46% for cells incubated at 100 μM. Changes in cell cycle distribution were also detected. Conclusions: Future study is warranted to determine if the addition of a COX-2 selective inhibitor will increase response rates and overall survival in a population of spontaneously arising canine nasal squamous cell carcinomas.
Growth rate of the bathypelagic crustacean Gnathophausia ingens (Mysidacea: Lophogastridae). I. Dimensional growth and population structure

Gnathophausia ingens has 13 instars, each with a distinct range of sizes which does not overlap the sizes of adjacent instars. The intermolt interval, measured in the laboratory at 5.5°, 6.5° and 7.5°C, increases with increasing size and decreases with increasing temperature. At 5.5°C it varies from 166 days for the smallest individuals to 253 days for the oldest. The period of larval development in the marsupium of a female is estimated to be 530 days. The life span of females is estimated to be 2,950 days with the onset of reproduction at 2,400 days. It is sugquested that this species is semelparous. The population structure data suggest that there is low mortality through the first 7 instars, progressively higher mortality from Instar 8 through Instar 11, and slightly lower mortality in the remaining 2 instars. These life-history characteristics appear to be directed toward maximizing absolute fecundity (as opposed to time-specific fecundity) in a stable environment. These characteristics may have been selected for by low available food energy and made possible by the stability of the deep sea.
Black residential segregation since the 1948 Shelley V. Kraemer decision

On May 3, 1948, the U.S. Supreme Court ruled that "private agreements to exclude persons of designated race or color from the use or occupancy of real estate for residential purposes do not violate the Fourteenth Amendment, but it is violative of the equal protection clause of the Fourteenth Amendment for state courts to enforce them" (Shelley v. Kraemer, 1948, p. 1). The U.S. Supreme Court decision overruled the decision of two state supreme courts in Missouri and Michigan. The Missouri Supreme Court held that a restrictive covenant barring Shelley and other Blacks from ownership of property in the city of St. Louis was an effective agreement and that enforcement of its provisions violated no rights guaranteed to Blacks by the federal Constitution (Kraemer v. Shelley, 1946). The circumstances presented in the Michigan case are similar to those in the Missouri case. The Michigan Supreme Court decided against the contentions made by Blacks in Detroit that they had been denied rights protected by the Fourteenth Amendment when a restrictive agreement had been signed that barred Blacks from ownership of property located in a section of that city (Sipes v. McGhee, 1947). There is little doubt that such restrictions on Black ownership of property had the effect of segregating Blacks to certain sections of cities prior to 1948. The purpose of this article is to assess the state of Black residential segregation since Shelley v. Kraemer. The focus
Microflare heating of the galactic halo

Recent estimates of the strength of the random component of the galactic magnetic field suggest that magnetic reconnection is probably important in heating the galactic halo. A microflare model of impulsive energy release has been proposed for the solar corona by Sturrock and collaborators. When the solar microflare model is scaled to a heating rate and pressure appropriate to the galactic halo, it predicts soft X-ray background emission, column densities of highly ionized species, and diffuse UV line emission in reasonable agreement with observed values. Column densities and surface brightnesses of low-ionization species are more ambiguously predicted by the model, but magnetic heating could contribute to them as well.
Picard Groups, Grothendieck Rings, and Burnside Rings of Categories

Abstract We discuss the Picard group, the Grothendieck ring, and the Burnside ring of a symmetric monoidal category, and we consider examples from algebra, homological algebra, topology, and algebraic geometry.
Reduction of pulmonary edema after SAH with a pulmonary artery catheter-guided hemodynamic management protocol.

Introduction: The frequency of pulmonary edema, which occurs with high frequency following subarachnoid hemorrhage (SAH), can be worsened by hypervolemic, hypertensive, hemodilution therapy for vasospasm. This study compares the complication rates for patients with SAH before and after institution of a pulmonary artery catheter-guided hemodynamic management protocol. Methods: Complication and outcome data were prospectively collected on 453 patients with spontaneous SAH. The patients were divided into groups treated from July 1998 through January 2000 (n=174) and from February 2002 through June 2002 (n=279). In group I, treatment consisted of hypervolemia (central venous pressures: >8 mmHg) and hypertension (mean arterial pressure: 110–130 mmHg). In group II, normovolemia was the goal, defined using a pulmonary artery catheter (wedge pressure: 10–14 mmHg). Cardiac output was enhanced (index: >4.5 L/minute/m2), and blood pressure elevations were moderated (mean pressure: >100 mmHg). Results: The average age, comorbidity, hemorrhage severity, and incidence of vasospasm were almost identical between the two groups. Statistically significant reductions were noted in patients in group II for two types of complications as well as for mortality. The rate of pulmonary edema (from 14 to 6%) and the rate of sepsis (from 14 to 6%) were both decreased (p≤0.03). Mortality decreased from 34 to 29% (p=0.04). Other complications, such as myocardial infarction, were not affected. Conclusions: These data show that a significant reduction in the frequency of pulmonary edema after SAH can be attained using a pulmonary artery catheter-guided hemodynamic management protocol.
Hemoglobin inhibits endothelium-dependent relaxation to acetylcholine in human coronary arteries in vivo.

BACKGROUND The endothelium can regulate vascular tone by releasing both endothelium-derived relaxing factor (EDRF or nitric oxide) and contracting factors. To date, there has only been circumstantial evidence to indicate EDRF activity in vivo in human coronary arteries. Using human hemoglobin as a specific inhibitor, the hypothesis that acetylcholine-induced coronary vasodilation is due to EDRF release was tested. METHODS AND RESULTS We studied the response of normal coronary arteries to acetylcholine (an endothelium-dependent vasodilator) and isosorbide dinitrate (an endothelium-independent vasodilator) in seven patients. The specificity of any vasodilator response was assessed by the infusion of reduced free human hemoglobin. Hemoglobin 10(-5) M infusion alone had no effect on coronary artery diameter. Drugs were infused into the coronary artery, and the diameter changes were assessed by quantitative angiography. Acetylcholine 10(-7) M increased left anterior descending coronary artery diameter from control: 2.30 +/- 0.12 mm to 2.79 +/- 0.20 mm (mean +/- SEM, n = 7, p CONCLUSIONS Using a specific inhibitor of nitric oxide, reduced free hemoglobin, we have demonstrated that basal EDRF release does not appear to play an important role in the maintenance of human epicardial coronary artery diameter in vivo but is responsible for the acetylcholine-induced dilatation.
Attitudes, Experiences, and Self‐Perceptions of Heroin Addicted Mothers

This study compares the mothering attitudes, experiences and self-perceptions of 170 women in treatment for heroin addiction with those of 175 non-addicted women of similar socio-economic status. The interviews reveal very little difference between addicted mothers and their non-addicted counterparts in their perceptions of how having children changes a woman's life, the nicest and worst things about having children, and good and bad reasons for having children. Addicted and non-addicted mothers do not differ in their feelings toward and perceptions of their own children, nor in most of the activities they engage in with their children. Heroin addicted mothers express more doubts about their adequacy as mothers and their ability to control or influence their children. Concerns about maternal adequacy pervade their responses. Addicted women receive as much social support for childrearing as non-addicted women, but rely more often than non-addicted women on their own mothers for assistance. A significant number of the addicted women bore children before they began using heroin suggesting that researchers and treatment personnel should emphasize needs of older children and their addicted mothers as well as problems of fetuses and neonates exposed to heroin in utero. Suggestions for treatment programs are made.
Axial head rotation increases facet joint capsular ligament strains in automotive rear impact.

Axial head rotation prior to low speed automotive rear impacts has been clinically identified to increase morbidity and symptom duration. The present study was conducted to determine the effect of axial head rotation on facet joint capsule strains during simulated rear impacts. The study was conducted using a validated intact head to first thoracic vertebra (T1) computational model. Parametric analysis was used to assess effects of increasing axial head rotation between 0 and 60° and increasing impact severity between 8 and 24 km/h on facet joint capsule strains. Rear impacts were simulated by horizontally accelerating the T1 vertebra. Characteristics of the acceleration pulse were based on the horizontal T1 acceleration pulse from a series of simulated rear impact experiments using full-body post mortem human subjects. Joint capsule strain magnitudes were greatest in ipsilateral facet joints for all simulations incorporating axial head rotation (i.e., head rotation to the left caused higher ligament strain at the left facet joint capsule). Strain magnitudes increased by 47–196% in simulations with 60° head rotation compared to forward facing simulations. These findings indicate that axial head rotation prior to rear impact increases the risk of facet joint injury.
Impedances Seen by Relays During Power Swings With and Without Faults

WE are at present in a period of power-system development during which it is essential that the best use be made of manpower and materials. To meet this requirement, equipment must be re-evaluated and refinements made in the design of apparatus and methods of system control. Loads on existing lines must be increased with continuity of service maintained. Of vital importance at this time is a thorough understanding of the operation of distance relays. The characteristics of the relays, and the system impedances “seen” by them, determine their performance. If it is known exactly what impedances are seen by a system of relays, their performance during power swings, with or without a fault on the system, can be predicted; and more important, relays having characteristics best suited for specific applications can be selected.
Evidence of turn and salt bridge contributions to β-hairpin stability: MD simulations of C-terminal fragment from the B1 domain of protein G

We ran and analyzed a total of eighteen, 10 ns molecular dynamics simulations of two C-terminal beta-hairpins from the B1 domain of Protein G: twelve runs for the last 16 residues and six runs for the last 15 residues, G41-E56 and E42-E56, respectively. Based on their CalphaRMS deviation from the starting structure and the pattern of stabilizing interactions (hydrogen bonds, hydrophobic contacts, and salt bridges), we were able to classify the twelve runs on G41-E56 into one of three general states of the beta-hairpin ensemble: 'Stable', 'Unstable', and 'Unfolded'. Comparing the specific interactions between these states, we find that on average the stable beta-hairpin buries 287 A(2) of hydrophobic surface area, makes 13 hydrogen bonds, and forms 3 salt-bridges. We find that the hydrophobic core prefers to make some specific contacts; however, this core does not require optimal packing. Side-chain hydrogen bonds stabilize the beta-hairpin turn with strong stabilizing interactions primarily due to the carboxyl of D46 with contributions from T49 hydroxyl. Buoyed by the strength of the hydrophobic core, other hydrogen bonds, primarily main-chain, guide the beta-hairpin into registration by forming a loose network of interactions, making an approximately constant number of hydrogen bonds from a pool of possible candidates. In simulations on E42-E56, where the salt bridge closing the termini is not favored, we observe that all the simulations show no 'Stable' behavior, but are 'Unstable' or 'Unfolded'. We can estimate that the salt-bridge between the termini provides approximately 1.3 kcal/mol. Altogether, the results suggest that the beta-hairpin folds beginning at the turn, followed by hydrophobic collapse, and then hydrogen bond formation. Salt bridges help to stabilize the folded conformations by inhibiting unfolded states.
Ultra High-Resolution Anterior Segment Optical Coherence Tomography in the Diagnosis and Management of Ocular Surface Squamous Neoplasia

The development of optical coherence tomography (OCT) technology has helped to usher in a new era of in vivo diagnostic imaging of the eye. The utilization of OCT for imaging of the anterior segment and ocular surface has evolved from time-domain devices to spectral-domain devices with greater penetrance and resolution, providing novel images of anterior segment pathology to assist in diagnosis and management of disease. Ocular surface squamous neoplasia (OSSN) is one such pathology that has proven demonstrable by certain anterior segment OCT machines, specifically the newer devices capable of performing ultra high-resolution OCT (UHR-OCT). Distinctive features of OSSN on high resolution OCT allow for diagnosis and differentiation from other ocular surface pathologies. Subtle findings on these images help to characterize the OSSN lesions beyond what is apparent with the clinical examination, providing guidance for clinical management. The purpose of this review is to examine the published literature on the utilization of UHR-OCT for the diagnosis and management of OSSN, as well as to report novel uses of this technology and potential directions for its future development.
THE RESPONSE OF TOBACCO TO SEEDBED APPLICATION OF DIPHENAMID

Summary. Seeds of three tobacco Nicotiana tabacum L.) varieties were soaked in water for 0, 1, 3 or 5 days and treated, after sowing in glasshouse flats, with NN-dimethyl-αα-diphenylacetamide (diphenamid) at 4·5 kg/ha 1, 3 or 5 days after sowing or at the cotyledonary stage. Unsprayed series were included as controls. Diphenamid caused thinning of seedlings in all varieties, but one (Maryland Catterton) showed some tolerance. All varieties showed stunting and malformations from diphenamid, particularly when seeds soaked for 5 days were treated either 1 or 5 days after sowing.
Protein Oxidation of Cytochrome c by Reactive Halogen Species Enhances Its Peroxidase Activity

Reactive halogen species (RHS; X(2) and HOX, where X represents Cl, Br, or I) are metabolites mediated by neutrophil activation and its accompanying respiratory burst. We have investigated the interaction between RHS and mitochondrial cytochrome c (cyt c) by using electrospray mass spectrometry and electron spin resonance (ESR). When the purified cyt c was reacted with an excess amount of hypochlorous acid (HOCl) at pH 7.4, the peroxidase activity of cyt c was increased by 4.5-, 6.9-, and 8.6-fold at molar ratios (HOCl/cyt c) of 2, 4, and 8, respectively. In comparison with native cyt c, the mass spectra obtained from the HOCl-treated cyt c revealed that oxygen is covalently incorporated into the protein as indicated by molecular ions of m/z = 12,360 (cyt c), 12,376 (cyt c + O), and 12,392 (cyt c + 2O). Using tandem mass spectrometry, a peptide (obtained from the tryptic digests of HOCl-treated cyt c) corresponding to the amino acid sequence MIFAGIK, which contains the methionine that binds to the heme, was identified to be involved in the oxygen incorporation. The location of the oxygen incorporation was unequivocally determined to be the methionine residue, suggesting that the oxidation of heme ligand (Met-80) by HOCl results in the enhancement of peroxidase activity of cyt c. ESR spectroscopy of HOCl-oxidized cyt c, when reacted with H(2)O(2) in the presence of the nitroso spin trap 2-methyl-2-nitrosopropane (MNP), yielded more immobilized MNP/tyrosyl adduct than native cyt c. In the presence of H(2)O(2), the peroxidase activity of HOCl-oxidized cyt c exhibited an increasing ability to oxidize tyrosine to tyrosyl radical as measured directly by fast flow ESR. Titration of both native cyt c and HOCl-oxidized cyt c with various amounts of H(2)O(2) indicated that the latter has a decreased apparent K(m) for H(2)O(2), implicating that protein oxidation of cyt c increases its accessibility to H(2)O(2). HOCl-oxidized cyt c also displayed an impaired ability to support oxygen consumption by the purified mitochondrial cytochrome c oxidase, suggesting that protein oxidation of cyt c may break the electron transport chain and inhibit energy transduction in mitochondria.
Quality of life among long-term survivors of breast cancer: Different types of antecedents predict different classes of outcomes.

Quality of life (QOL) has many aspects, both in the short-term and in the long-term. Different aspects of QOL may have different types of precursors: demographic, medical, and psychosocial. We examined this possibility in a group of long-term breast cancer survivors. Early-stage breast cancer patients (N=163) who had provided information about medical, demographic, and psychosocial variables during the year after surgery completed a multidimensional measure of QOL 5–13 years later. Initial chemotherapy and higher stage predicted greater financial problems and greater worry about appearance at follow-up. Being partnered at diagnosis predicted many psychosocial benefits at follow-up. Hispanic women reported greater distress and social avoidance at follow-up. Initial trait optimism predicted diverse aspects of better psychosocial QOL at follow-up, but not other aspects of QOL. Thus, different aspects of QOL at long-term follow-up had different antecedents. Overall, psychological outcomes were predicted by psychosocial variables, presence of a partner at diagnosis, and ethnicity. Financial outcomes, in contrast, were predicted by medical variables, which otherwise predicted little about long-term QOL. This divergence among aspects of QOL should receive closer attention in future work. Copyright © 2005 John Wiley & Sons, Ltd.
Finite element method for the solution of Maxwell's equations in multiple media

This paper concerns a subdomain collocation finite element method which is applied to solve the electromagnetic equations with two or more media. The solution is discontinuous. Both the implementation and the proof of convergence are discussed.
Analysis of quadric-surface-based solid models

The author discusses data representations and analytical tools commonly used in solid modelers for three analysis operations: boundary evaluation, image generation, and mechanical property calculation. The methods described are generally applicable to solid models bounded by quadric surfaces (e.g. planes, cylinders, spheres, and cones). Only methods applicable to constructive solid geometry or boundary representation modelers are considered. The author concludes with a review of ongoing research into other analysis operations appropriate for solid modeling representations. >
Caudate-induced inhibition of hypothalamic attack behavior

Low-frequency caudate stimulation in four cats inhibited the somatic motor directed components Of hypothalamic aggression. The autonomic and reflexive aspects of attack were unaffected by the synchronogenic stimulation. These results, in conjunction ' with previous findings on caudate inhibition, indicate that low-frequency caudate activation interferes with elaboration of goal-<lirected behavior. Previously, the caudate nucleus was found to be part of a system which modulated the ascending reticular activating system (Buchwald, Wyers, Lauprecht, & He-user, 1961; Heuser, Buchwald, & Wyers, 1961). Electrical stimulation of the caudate nucleus influenced the arousal level of cats. High-frequency stimulation (over 30 pps) caused behavioral activation, while low-frequency stimulation (0.2-10 pps) induced a state of general inhibition and eventually caused sleep (Buchwald, Wyers, Lauprecht, & Heuser, 1961). Recently, the inhibitory consequences oflow-frequency caudate stimulation have been observed in a variety of instrumental conditioning situations. Rather than producing a state of general inhibition, caudate activation was found to have strong inhibitory influences on tasks which were complex, recently, or incompletely learned. Simple and overlearned reactions were much less susceptible to being inhibited (Buchwald & Hull, 1967; Buser, Rougeul, & Perret, 1964; Kitsikis & Rougeul, 1968; Peeke & Herz, 1971; Wyers, Peeke, Williston, & Herz, 1968). Many instrumentally conditioned behaviors have been investigated during the application of low-frequency caudate . stimulation. However, there has not been a systematic investigation of behaviors which are automatic in nature and do not depend upon learning. The purpose of the present study was to determine if synchronogenic caudate stimulation would also . have inhibitory influences on innately organized patterns of behavior. Hypothalamic stimulation was used to elicit affective and stalking attack reactions. These behaviors were similar if not the same as those elicited by naturally occurring stimuli (Wasman & Flynn, 1962; Levison & Flynn, 1965) and appeared to be innately organized (Roberts & Bergquist, 1968). The inhibition of these well-controlled intense reactions would allow a severe test of the influence of low-frequency caudate stimulation.
Soft X-ray emission excited by electron beams in a superlattice

Abstract High-energy electrons emit resonant electromagnetic radiation when passing through a spatially periodic medium. It is conventionally assumed that ultra-relativistic electron beams are required to obtain significant emission. We demonstrate theoretically the feasibility of exploiting solid-state superlattices with short spatial periods to obtain both spontaneous and stimulated emission in the extreme-ultraviolet and soft X-ray range using non-relativistic beams. Both classical and quantum approaches are developed.
Beyond the rodent model: Calorie restriction in rhesus monkeys

Lifespan extension and reduction of age-related disease by calorie restriction (CR) are among the most consistent findings in gerontological research. The well known effects of CR have been demonstrated many times in rodents and other short-lived species. However, effects of CR on aging in longer-lived species, more closely related to humans, were unknown until recently. Studies of CR and aging using nonhuman primates (rhesus monkeys) were begun several years ago at the National Institute on Aging, the University of Wisconsin-Madison, and the University of Maryland. These studies are beginning to yield useful data regarding the effects of this nutritional intervention in primates. Several studies from these ongoing investigations have shown that rhesus monkeys on CR exhibit physiological responses to CR that parallel findings in rodents. In addition, several potential biomarkers of aging are being evaluated and preliminary findings suggest the possibility that CR in rhesus monkeys could slow the rate of aging and reduce age-related disease, specifically diabetes and cardiovascular disease. It will be several years before conclusive proof that CR slows aging and extends life span in primates is established, however, results from these exciting studies suggest the possibility that the anti-aging effects of CR reported in rodents also occur in longer-lived species such as nonhuman primates, strenghtening the possibility that this nutritional intervention will also prove beneficial in longer-lived species, including humans.
Direct visualization of electrophoretic mobility shift assays using nanoparticle-aptamer conjugates.

Here we demonstrate that aptamers tethered to gold nanoparticles enable direct visualization of protein-oligonucleotide interactions during gel electrophoresis. This technique is used to confirm that an aptamer previously identified as binding to C-reactive protein (CRP) only binds to the monomeric form of CRP. While native, pentameric CRP (pCRP) is used in clinical assays to predict cardiovascular disease (CVD) risk, it is the monomeric isoform that is more strongly associated with pro-inflammatory and pro-atherogenic effects. To visualize this selectivity, the CRP-aptamer was conjugated to streptavidin-coated gold nanoparticles and the mobility of the free oligonucleotide-nanoparticle conjugate (ON-NP) and the protein/ON-NP complex bands were visualized and recorded during electrophoresis using a simple digital camera. At a concentration of 6 mg/mL, monomeric CRP showed a significant decrease in the observed ON-NP mobility, whereas no change in mobility was observed with pCRP up to 18 mg/mL. Advantages of this nanoparticle-based electrophoretic mobility shift assay (NP-EMSA) over traditional EMSA include real-time detection of protein-oligonucleotide interactions, the avoidance of harmful radioisotopes, and elimination of the need for expensive gel imagers. The availability of both the NP-EMSA technique and an mCRP specific probe will allow for improved clinical diagnostic to more accurately predict future CVD risk.
A Low Power X-Ray Diffractometer for Soil Analysis in Remote Locations Employing a Multiwire Proportional Counter Detector Array

A low power x-ray powder diffraction system suitable for remote mineralogical analysis of lunar, planetary, or asteroid soils has been designed. A one Curie 55Fe source provides a monochromatic x-ray beam of 5.9 keV. Seeman-Bohlin or focusing geometry is employed in the camera, allowing peak detection to proceed simultaneously at all angles and obviating the need for moving parts. The detector system is an array of 500-600 proportional counters with a wire-spacing of 1 mm. An electronics unit comprising preamplifier, postamplifier, window discriminators and storage flip-flops requiring only 3.5 milliwatts has been designed and tested. Total instrument power is less than 5 watts. Powder diffraction patterns using a flat breadboard multiwire counter have been recorded.
Cytomegalovirus prophylaxis with ganciclovir and cytomegalovirus immune globulin in liver and intestinal transplantation.

Liver and intestinal transplant recipients at the University of Miami receive an intensive regimen of cytomegalovirus (CMV) prophylactic therapy consisting of a combination of CMV immune globulin intravenous (CMV-IGIV, CytoGam®) and ganciclovir. The 5-year experience with this regimen in liver transplant patients showed effective CMV prophylaxis in this patient population. The importance of an effective prophylactic strategy was underscored by higher observed rates of chronic rejection and post-transplant lymphoproliferative disorder (PTLD) in CMV-infected patients. The use of CMV-positive donors for intestinal transplants did not increase the incidence of CMV disease. Intestinal transplant recipients had improved survival rates, reflecting an aggressive policy of monitoring, immunosuppression, and CytoGam® plus ganciclovir prophylaxis.
Pharmacokinetics of continuous-infusion amsacrine and teniposide for the treatment of relapsed childhood acute nonlymphocytic leukemia.

The systemic disposition of both amsacrine and teniposide was determined in children receiving treatment for resistant acute nonlymphocytic leukemia. As part of a phase I–II study, amsacrine and teniposide were given as continuous 72-h i.v. infusions at doses of 75–150 and 150–250 mg m−2 day−1, respectively. Plasma samples obtained during steady state were analyzed for drug concentrations by high-performance liquid chromatography assays specific for each compound. Clearance and systemic exposure values for both amsacrine and teniposide were calculated for 14 patients, and data were available for teniposide alone in an additional 14 subjects. Interpatient variability in clearance was substantial for each drug, producing overlapping systemic exposure across dose levels. No evidence of dose-dependent drug clearance was evident. Clearance values for teniposide given in combination with amsacrine were similar to previous values obtained when teniposide was given in an identical manner but as a single agent. In all, 80% of patients experienced some degree of mucositis after chemotherapy administration. Severe mucositis (Pediatric Oncology Group grades 3–4) occurred in 18% of cases, all of whom showed teniposide steady-state plasma concentrations above the median population value (11.9 μg/ml;P<0.0001). A comparison of the results of the present study on teniposide combined with amsacrine with those previously obtained for single-agent teniposide suggest that amsacrine produced little additive gastrointestinal toxicity. The evaluation of anticancer drug pharmacokinetics in individual patients during combination chemotherapy regimens helps to determine the relative importance of each agent when toxicity patterns are similar.
Military‐civilian humanitarianism: The ‘age of innocence’ is over

In the 1990s the UN has been unable to ignore emergencies within war‐torn societies. It has been overstretched by new and complex ‘peacekeeping’ commitments, and has tended to subcontract to major states, regional organizations and NGOs to provide services. Difficulties frequently arise between humanitarians and military forces because of their different and sometimes conflicting objectives and modes of operation in complex emergencies. Seven categories of operation are identified where civilian humanitarians and military forces interact and co‐operate. They demonstrate that humanitarianism has been politicized and suggest that, under certain circumstances, civilian humanitarians will be obliged to temper traditional principles of neutrality and impartiality. A new reality has emerged which recognizes that humanitarian action does not occur in a political vacuum. In effect there has been a ‘loss of innocence’ on the part of agencies and humanitarians engaged in providing assistance to afflicted peoples.
Response to selection for early spawn date in rainbow trout, Salmo gairdneri

Abstract The effectiveness of selection for early spawn date was determined for two year-classes of two rainbow trout broodstocks spawning at 2 years of age based on female spawning date. One stock was selected for early spawn date, and one was bred to maintain the existing spawn date. Average response in the selected stock was nearly 7 days per generation through six generations of selection. Assuming that selection differentials for males were equal to those observed for females, realized heritability estimates for spawn data were 0.55 ± 0.07 and 0.53 ± 0.05 for the two yearclasses. The broodstock bred to maintain spawn date showed no linear response, but there was cyclic variation in spawn date from generation to generation. Careful examination of the data suggested that the realized heritability estimate may be biased upward due to influences of management and selection involving other traits. Therefore, the estimates should be considered as the upper limit when predicting response to selection under commercial conditions. Also, there was some evidence of a negative effect of early spawning on egg size.
Technical visualizations in VLSI design: visualization

Visualization techniques were applied to several different types of VLSI design and simulation data. A number of different visualizations have been tried, with varying results. Examples include 3D visualization of voltage and currents from fullwave interconnect analysis, on-chip clock distribution networks, chip/package power supply noise analysis, wire congestion, chip layout imaging, and static circuit tuning. The goals, successes, and failures of these examples will be discussed, along with some unexpected benefits from our ability to easily see patterns in complex visualizations.
Radiographic Abnormalities of the Lumbar Spine in College Football Players A Comparative Analysis

The purpose of this study was to make a direct comparison between lumbar spine radiographs of incoming college football players and of an age-matched control group to determine whether there is a higher prevalence of lumbar spine abnormalities in football players before competing at the Division I level. We reviewed 187 lumbar spine radiographs. Of these, 104 were taken as a standard part of the preparticipation physical examination for incoming college football players. The remaining 83 radiographs were taken during routine preemployment physicals at a local factory. Each radiograph was read independently by three separate orthopaedic radiologists in a blinded fashion. Data were collected and statistically evaluated for 13 variables. The rate of spondylolysis was only 4.8% in our group of athletes and 6.0% in the control group (not significantly different). Only in the category of degenerative changes was a significant difference found. The control group had a 16.9% incidence of disk space narrowing and ...
Clozapine Increases EEG Photic Driving in Clinical Responders

Photically driven electroencephalography was tested in 17 chronic schizophrenia patients who were treated with clozapine for 5 weeks. Eight of the 17 patients showed clinical improvement on the Brief Psychiatric Rating Scale (delta BPRS > 30%) while the other 9 patients remained unchanged (delta BPRS < 15%). In comparison with the nonresponders, clozapine responders had a significantly greater increase in photic driving in the electroencephalogram (EEG), primarily in the low-frequency range of alpha band (7.2 hertz [Hz], 8.3 Hz, 9.0 Hz, and 9.6 Hz, but not 12.0 Hz). The difference in the resting EEG between the responders and nonresponders did not reach statistical significance. These findings suggested that EEG photic driving might be more sensitive than the resting EEG in detecting the central nervous system drug effect. Further analysis revealed that the increase of EEG photic driving was positively correlated with patients' clinical improvement. Combined with our previous observation in the drug-free schizophrenia patients who had lower EEG photic driving, present results supported the hypothesis that the amount of EEG alpha activity, particularly its synchronization to the external stimuli, could reflect the thalamic function in sensory information processing in schizophrenia.
Postural Adaptations To Supra-postural Tasks in Children With Developmental Coordination Disorder

We investigated the effect of varying memory (cognitive) demands, and visual (perceptual) demands on postural motion. Sixty four children (32 DCD, 32 TDC, 9-to-10 years) were volunteers. Each performed separate memory and visual tasks at two levels of difficulty; easy (LD) and hard (HD) while recording their postural motion. For the memory task, both groups reduced postural sway in the HD condition. For the visual task only the TDC group reduced postural sway in the HD condition; DCD children did not. The DCD group did not reduce postural motion but, in fact, increased motion. We also found several group u task interactions on sway. Our data suggest a weakening of the action linkage between both cognitive and perceptual tasks in children diagnosed with movement difficulties. The data are discussed in the context of limitations in the embodied relationship between posture and both perceptual and cognitive activity.
Dose escalation trial designs based on a molecularly targeted endpoint.

Traditional phase I dose-finding studies for chemotoxic agents base dose escalation on toxicity, with escalation continuing until unacceptable toxicity is observed. Recent development of molecularly targeted agents that have little or no toxicity in the therapeutic dose range has raised questions over the best study designs for phase I studies. Two types of designs are proposed and evaluated in this paper. In these designs, escalation is based on a binary response that indicates whether or not the agent has had the desired effect on the molecular target. One design is developed to ensure that if the true target response rate is low there will be a high probability of escalating and if the true target response rate is high there will be a low probability of escalating. The other design is developed to continue to escalate as long as the true response rate is increasing and to stop escalating when the response rate plateaus or decreases. A limited simulation study is performed and the designs are compared with respect to the dose level at the end of escalation and the number of patients treated on study. Published in 2005 by John Wiley & Sons, Ltd.