cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract P5-06-12: Roscovitine Confers Tumor Suppressive Effect on Therapy-Resistant Breast Tumor Cells

Background: Current clinical strategies for treating hormonal breast cancer involve the use of antiestrogens (AE) that block ERα functions, and aromatase inhibitors (AI) that decrease local and systemic estrogen production. Both of these strategies improve outcomes for ER+ve breast cancer; however development of therapy resistance is a major clinical problem. E merging data implicate ER-signaling cross talk, and alteration in ER subtypes as the major causes of resistance. Current evidence suggest that ERa increases proliferation, while ERα decreases cell proliferation and the ratio between ERα and ERα is the driving force for tumor cell proliferation. Further, most downstream events in the resistance pathways converge upon modulation of cell cycle regulatory proteins; the most conspicuous of which is the activation of Cyclin Dependent Kinase 2 (CDK2) pathway. Roscovitine is one of the most frequently studied andused CDK2 inhibitor. In this study, we examined whether Roscovitine confers tumor suppressive advantage to therapy resistant breast epithelial cells by inhibiting CDK functions. Methods: We tested the effect roscovitine using three different therapy resistant model cells; (a) MCF-7-Tam (acquired Tamoxifen resistance model); (b) MCF-7-LTLT-ca (acquired Letrozole resistance model); (c) MCF-7-HER2 that exhibit Tamoxifen resistance (ER-growth factor signaling cross talk model). Cells were treated with Roscovitine (0-30 uM) for 24 hours and proliferation was measured after 48h using a luminescent cell viability assay (Promega). CDK activity, expression of ERα, β subtypes, ER-coregulators, and expression of ER target genes was measured by Western and PCR assays. To test the efficacy of Roscovitine in vivo, pre-clinical nude mice models bearing xenografts of therapy resistant cells were subjected to orally available Roscovitine (100mg/kg/tid/oral) for 10 days or treated with vehicle and tumor growth was monitored for a further 15 days. Results: The results showed that Roscovitine (10uM) significantly inhibited the growth of all three therapy resistant cells in cell proliferation and foci formation assays (P Conclusions: Our results suggest that Roscovitine can be used to inhibit the growth of therapy resistant cells. Since many advanced and therapy resistant tumors exhibit loss or reduced expression of ERα, dual action of Roscovitine will provide a novel drug to inhibit both CDKs and to increase the expression of tumor suppressor ERα, thus has potential to serve as a double-edged sword to interfere with the resistance mechanisms. Supported by DOD Fellowship W81XWH-09-1-0010 (BCN) and NIH grant CA095681(RV). Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-06-12.
Unusual chest radiographic findings in children

A 9-year-old British Asian girl with asthma was referred by her general practitioner to outpatients with a 12-month history of dry cough and an abnormal chest radiograph. There was no history of recent …
Monsoonal moisture sources revealed using temperature, precipitation, and precipitation stable isotope timeseries

Results of analyses using timeseries of mean temperature, precipitation amount, and stable isotopes from precipitation from July–August in Tucson, Arizona, have revealed atmospheric circulation patterns related to the North American Monsoon in the U.S. Southwest. The isotope timeseries and Tucson air temperatures and precipitation amount are significantly correlated. The temperature and isotope timeseries also correlate significantly with regional and extra-regional specific humidity, and with Eastern Pacific SSTs near the Mexican coast, evidence for a dominantly Pacific/Gulf of California summer moisture source for the period 1983–1999. Separation of extra-regional wind vector datasets into groups of years matching relative isotopic depletion or enrichment of the Tucson July–August precipitation seasonal means for the stable isotope timeseries (usually the extreme years in the Tucson seasonal temperature means) suggest circulation patterns entraining more tropical moisture in cooler/isotopically depleted years, and entraining less tropical moisture in hotter/isotopically enriched years.
MATURATION OF THE MEIOSPORANGIA OF EUALLOMYCES. II. PRELIMINARY OBSERVATIONS ON THE EFFECT OF AUXINS

THE SPOROPHYTIC GENERATION of the water molds in the subgenus Euallomyces bears thick-walled, pitted, brown meiosporangia which ultimately give rise to an independent gametophytic generation. When the sporophyte is grown on nutrient agar slants, the sporangia develop immediately behind the growing front so that the slant appears brown. An individual sporangium acquires its characteristic morphology and color in 48-72 hr. after initiation. At this time each meiosporangium contains about a dozen diploid nuclei and numerous spherical, orceinstaining bodies called chromospheres. They are, however, immature because they will not germinate when placed in water. If the slants are stored at room temperature in the laboratory for 2 weeks to two or more months, depending on the strain, a process of maturation takes place within the sporangia. If then, the mature structures are placed in water they germinate with the discharge of approximately 4 dozen motile, haploid, uninucleate meiospores each of which develops directlv into a gametophytic plant (see Emerson, 1941 or Sparrow, 1943 for the detailed life cycle, and Emerson and Wilson, 1949 and Wilson, 1952 for the nuclear cycle). The purposes of this study and the preceding one (Machlis and Ossia, 1953) were to find methods for shortening the period of maturation and to learn what is involved in the process of maturation. Emerson and Wilson (Wilson, 1952) made the important observation that a mature sporangium was characterized by the absence of chromospheres and the presence of nuclei in an advanced prophase of meiosis I. They postulated that the attainment of maturity, i.e., germinability, was equivalent to the disappearance of the chromospheres and the concomitant appearance of late prophase nuclei. Such mature meiosporangia can be stored dry for many years. Upon immersion in water, meiosis resumes, the content swells with a consequent cracking of the thick, outer wall, cleavage takes place, and the meiospores are discharged. Machlis and Ossia (1953) confirmed the fact that no sporangia become mature until the chromospheres disappear. They showed that the digestion of the chromospheres occurs rapidly. For example, in one series of observations of sporangia developed and matured on agar, chromospheres were evident for 23 days in over 90 per cent of the sporangia; 24 hr. later over 90 per cent of the sporangia were without chromospheres. Simultaneous with the disappearance of the chromospheres, germinability also abruptly increases
Health care access dimensions and cervical cancer screening in South Africa: analysis of the world health survey

Background: Cervical cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality among women in sub-Saharan Africa. Recent recommendations for cervical cancer primary prevention highlight HPV vaccination, and secondary prevention through screening. However, few studies have examined the different dimensions of health care access, and how these may influence screening behavior, especially in the context of clinical preventive services. Methods: Using the 2003 South Africa World Health Survey, we determined the prevalence of cervical cancer screening with pelvic examinations and/or pap smears among women ages 18 years and older. We also examined the association between multiple dimensions of health care access and screening focusing on the affordability, availability, accessibility, accommodation and acceptability components. Results: About 1 in 4 (25.3%, n = 65) of the women who attended a health care facility in the past year got screened for cervical cancer. Screened women had a significantly higher number of health care providers available compared with unscreened women (mean 125 vs.12, p-value <0.001), and were more likely to have seen a medical doctor compared with nurses/midwives (73.1% vs. 45.9%, p-value = 0.003). In multivariable analysis, every unit increase in the number of health care providers available increased the likelihood of screening by 1% (OR = 1.01, 95% CI: 1.00, 1.01). In addition, seeing a nurse/midwife compared to a medical doctor reduced the likelihood of screening by 87% (OR = 0.13, 95% CI: 0.04, 0.42). Conclusions: Our findings suggest that cost issues (affordability component) and other patient level factors (captured in the acceptability, accessibility and accommodation components) were less important predictors of screening compared with availability of physicians in this population. Meeting cervical cancer screening and HPV vaccination goals will require significant investments in the health care workforce, improving health care worker density in poor and rural areas, and improved training of the existing workforce.
Anatomy of the bilioduodenal junction of the opossum.

Prevention of reflux is a major function of the terminal biliary duct system at its junction with the duodenum. We examined this area via scanning electron microscopy and light microscopy to explore anatomic features that might play such a role in the Virginia opossum, a species with a highly developed sphincter of Oddi (SO). The terminal apparatus, most of which consists of a dilated extramural ampulla, has a lumen with abundant folds. Mucus is produced by the lining epithelium and by a plethora of glands. Three muscle layers constitute the SO: an inner longitudinal, an outer circular, and a less consistent, outermost longitudinal. The terminal apparatus forms an acute angle and narrows as it enters the duodenum; at this point, the SO becomes continuous with the muscularis externa of the intestine. Four anatomical features with potential antireflux properties may be identified: mucus production, luminal folds, and the narrow opening and oblique course of the intramural duct.
Functional and morphological differentiation of nonpigmented ciliary body epithelial cells grown on collagen rafts

We have examined the effect of alteration in cell shape on promoting differentiated morphology and physiology in cultured nonpigmented epithelial cells from the ciliary body. We have grown pure populations of nonpigmented cells on collagen gels released from the culture dish to create collagen rafts. Shortly after the gels were detached, the cells shrank in diameter and increased in height while they contracted the gel. Concurrently, the actin cytoskeleton reorganized to the cell cortex as found in vivo. After this differentiated morphology developed, large changes in intracellular Ca2+ could be elicited by simultaneous activation of acetylcholine and epinephrine or acetylcholine and somatostatin receptors as seen in intact tissue. Explant cultures of isolated nonpigmented cell layers maintained their actin distribution and also showed synergistic Ca2+ increases. Spread cells, grown on rigid substrates, had a disorganized cytoskeleton and rarely showed synergism. These data suggest that the mechanism underlying synergistic Ca2+ responses in the ciliary body is functional in nonpigmented cells grown on collagen rafts. In addition, this pathway appears to be sensitive to the disposition of the cell’s cytoarchitecture.
Optical-rotation technique used for a high-precision measurement of parity nonconservation in atomic lead

We have measured the parity-nonconserving (PNC) optical rotation near the 1.279-\ensuremath{\mu}m $^{3}$${\mathit{P}}_{0}$${\ensuremath{\rightarrow}}^{3}$${\mathit{P}}_{1}$ magnetic-dipole absorption line in atomic lead vapor. We measure the quantity scrR\ensuremath{\equiv}Im(${\mathit{scrE}}_{\mathrm{PNC}}$/scrM), where scrM is the magnetic-dipole amplitude of the absorption line and ${\mathit{scrE}}_{\mathrm{PNC}}$ is the electric-dipole amplitude coupled into the same line by the PNC interaction within the lead atom. We find scrR to be (-9.86\ifmmode\pm\else\textpm\fi{}0.04\ifmmode\pm\else\textpm\fi{}0.11)\ifmmode\times\else\texttimes\fi{}${10}^{\mathrm{\ensuremath{-}}8}$, where the first error is statistical and the second is systematic. The statistical errors are due to incompletely subtracted background fluctuations, and the systematic errors are caused by line-shape uncertainties and calibration error. Our value is consistent with the atomic PNC calculations for lead, which give scrR=(-10.7\ifmmode\pm\else\textpm\fi{}0.8)\ifmmode\times\else\texttimes\fi{}${10}^{\mathrm{\ensuremath{-}}8}$ for the standard electroweak model with ${\mathrm{sin}}^{2}$${\mathrm{\ensuremath{\theta}}}_{\mathit{W}}$=0.23 and no electroweak radiative corrections. Including radiative corrections yields the value S=-3\ifmmode\pm\else\textpm\fi{}8 for the isospin-conserving electroweak parameter, with difficulties in the atomic theory of lead presently limiting the extent to which our result tests the standard model. This same technique can also be applied to thallium, where the atomic theory is currently accurate to 3%. By searching for a difference in scrR for the two hyperfine components of $^{207}\mathrm{Pb}$, we find the amplitude of the nuclear spin-dependent PNC rotation to be less than 2\ifmmode\times\else\texttimes\fi{}${10}^{\mathrm{\ensuremath{-}}2}$ of the nuclear spin-independent rotation.
Factors associated with recurrent back pain and cyst recurrence after surgical resection of one hundred ninety-five spinal synovial cysts: analysis of one hundred sixty-seven consecutive cases.

Study design Retrospective study. Objective Compare outcomes of different treatment methods for intraspinal synovial cysts. Summary of background data Intraspinal synovial cysts are cited as an increasing cause of back pain and radiculopathy. To date, few studies have compared outcomes of differing treatment methods in patients with synovial cysts. Methods We retrospectively reviewed 167 consecutive patients undergoing surgical management of 195 symptomatic synovial cysts at a single institution over 19 years. The incidence of postoperative mechanical back pain, radiculopathy, and cyst recurrence was compared between patients undergoing unilateral hemilaminectomy (n = 51), bilateral laminectomy (n = 39), facetectomy with in situ fusion (n = 18), and facetectomy with instrumented fusion (n = 56). Results A total of 155 (97.5%) patients presented with radiculopathy, 132(82.5%) with mechanical back pain, 31 (20%) with neurogenic claudication, and 5 (3.2%) with bladder dysfunction. Most cysts occurred in the lumbar spine. After surgery, back and radicular pain improved in 91.6% and 91.9% patients, respectively. By a mean follow-up of 16 +/- 9 months, 36 (21.6%) patients developed recurrent back pain, 20 (11.8%) recurrent leg pain, and 5 (3%) recurrent synovial cysts. Patients undergoing laminectomy had a significantly increased cyst recurrence incidence compared to fusion groups via log-rank test (P = 0.042), and this risk was decreased to baseline with instrumented fusion on reoperation. Laminectomy was also associated with the highest increased risk of recurrent back pain in both log-rank test (P = 0.018) and proportional hazards regression (HR): 1.64 (1.00-3.45), P = 0.05. Instrumented fusion had the lowest risk for back pain recurrence. Conclusion Hemilaminectomy or laminectomy remains one of the mainstay surgical treatments for symptomatic intraspinal synovial cysts. Our experience shows that the majority of patients undergoing decompression/excision of synovial cysts will have immediate improvement in back and leg pain. However, within 2 years, patients receiving hemilaminectomy or laminectomy alone have an increased incidence of back pain and cyst recurrence. Decompression with instrumented fusion appears to be associated with the lowest incidences of cyst recurrence or back pain.
Scaling behavior of deposition models with limited downward mobility.

We have studied the interface-width scaling behavior of deposition models in which limited downward mobility is introduced. In all the models studied here, there is a maximum allowed slope for the interface at which the growth velocity is zero. The Kardar-Parisi-Zhang equation is resummed in order to show explicitly this slope constraint, but still incorporates parameters \ensuremath{\lambda} measuring the slope dependence of the growth velocity, \ensuremath{\nu} measuring the surface tension, and D measuring the noise amplitude. Increasing mobility naturally smooths the interface, and is associated with a decrease in the magnitude of ${\ensuremath{\lambda}}_{\mathrm{eff}}$=\ensuremath{\lambda}${\mathit{D}}^{1/2}$/${\ensuremath{\nu}}^{3/2}$. A detailed study of a bridge-site deposition model, with one hop of probability p, shows that \ensuremath{\Vert}\ensuremath{\lambda}\ensuremath{\Vert} increases with p. From an independent assessment of noise-amplitude behavior, we can conclude that \ensuremath{\nu} must also increase with p to ensure the required ${\ensuremath{\lambda}}_{\mathrm{eff}}$ behavior. Direct determination of \ensuremath{\nu} via the Wolf-Tang procedure of imposing inhomogeneity on some length scale L supports this conclusion. (However \ensuremath{\nu} depends on the inhomogeneity strength, which should be chosen small, and on L.) We comment on anticipated behavior of similar limited-mobility models in d\ensuremath{\ge}2 dimensions, and compare with behavior of limited-mobility ballistic deposition and noise-reduced deposition models.
Nitrogen enrichment increases net silica accumulation in a temperate salt marsh

Two New England salt marshes exposed to different N availability were assessed seasonally for 1 yr, creating the first complete salt marsh Si budgets. Triplicate seasonal measurements were collected for aboveground biomass of dominant Spartina species (S. alterniflora Loisel. and S. patens (Aiton) Muhl.), belowground vegetation (roots and rhizomes), sediment, and pore water. Measured Si values (reported as SiO2) diverged in several respects to that of other wetlands. Biogenic Si (BSi) concentrations in S. alterniflora were . 1% of dry weight (dry wt), values higher than previously reported in a temperate salt marsh. Rhizomes had significantly less BSi than roots (0.45% and 1.24% dry wt in the rhizomes and roots, respectively). Roots at the high-N marsh had higher BSi concentrations (average 1.44 6 0.11% dry wt) than reported in other wetland plant species. Likewise, sediment amorphous Si (ASi) concentrations (. 12% ASi) were elevated compared with most other temperate wetlands, although the average (4.4% 6 0.5% ASi dry wt) was within the range of other reported values. A clear pattern toward more Si accumulation at the N-enriched salt marsh was found in the roots, sediment, and pore water, and occasionally in the aboveground vegetation. Unlike other aquatic systems, N enrichment does not result in salt marsh Si limitation, despite the presence of Si-accumulating organisms (marsh grasses). Increased soil respiration, sediment availability, and rates of organic matter decomposition are hypothesized to cause higher Si accumulation at the high-N marsh. This relationship was most pronounced in the summer for S. patens, leading us also to hypothesize that Si accumulation in marsh grasses may be related to temperature stress.
Effect of carrier molecules on production and properties of extracellular hemolysin produced byStreptococcus agalactiae

Streptococcus agalactiae type la strain 090 produced a cell-associated hemolysin during exponential growth in medium lacking proteins. Growth of the organism in medium containing proteins or medium supplemented with Tween 40 resulted in the appearance of extracellular hemolytic activity that was filterable. Maximum extracellular hemolytic activity was obtained in the late exponential phase of growth corresponding to the maximum number of cells. Extracellular hemolysin released in medium containing proteins could be precipitated by ammonium sulfate. Cell-associated hemolysin could be extracted in the cold by purified lipoteichoic acid from the organism. Purification and characterization of the extracellular hemolysin by column chromatography showed that the hemolysin was associated with molecules eliciting its release. Hemolysin associated with lipoteichoic acid or Tween 40 had an apparent molecular weight of 1,800,000 or 60,000 daltons, respectively.
Thin Bridges in Isotropic Electrostatics

Fast hierarchical methods for potential field evaluations have in recent years found interesting applications in computational physics and engineering. For example, these methods have been used in combination with integral equation methods for solving the electrostatic and elastostatic equations for materials with inclusions. A lingering obstacle on the way to constructing a general purpose algorithm for inclusion problems is the treatment of inclusion interfaces that lie very close to each other. The difficulty is to assess the need for resolution and to evaluate layer potentials close to their sources in a fast and accurate fashion. This paper presents an automated algorithm for such an assessment and evaluation. The robustness and speed of the algorithm is demonstrated through a series of examples involving thin bridges, coatings, narrow necks, corners, cusps, and random mixtures.
Separation of naturally occurring 3',5'-cyclic ribonucleotides using high pressure liquid chromatography.

Abstract A simple and fairly rapid procedure is described for separation of a mixture of five 3′, 5′-cyclic ribonucleotides. The separation was achieved by high pressure liquid chromatography on a Vydac pellicular anion exchange column using a linear gradient of 0.5 to 1.0 m acetic acid as the eluting solvent.
Affirmative Action, Cuban Style

Dr. Fitzhugh Mullan writes about the long-standing problem of insufficient diversity in the medical profession in the United States and about a school in Havana dedicated to training doctors to treat the poor of the Western hemisphere and Africa.
The nuclear localization of low risk HPV11 E7 protein mediated by its zinc binding domain is independent of nuclear import receptors.

Abstract We investigated the nuclear import of low risk HPV11 E7 protein using 1) transfection assays in HeLa cells with EGFP fusion plasmids containing 11E7 and its domains and 2) nuclear import assays in digitonin-permeabilized HeLa cells with GST fusion proteins containing 11E7 and its domains. The EGFP-11E7 and EGFP-11cE7 39–98 localized mostly to the nucleus. The GST-11E7 and GST-11cE7 39–98 were imported into the nuclei in the presence of either Ran-GDP or RanG19V-GTP mutant and in the absence of nuclear import receptors. This suggests that 11E7 enters the nucleus via a Ran-dependent pathway, independent of nuclear import receptors, mediated by a nuclear localization signal located in its C-terminal domain (cNLS). This cNLS contains the zinc binding domain consisting of two copies of Cys-X-X-Cys motif. Mutagenesis of Cys residues in these motifs changed the localization of the EGFP-11cE7/-11E7 mutants to cytoplasmic, suggesting that the zinc binding domain is essential for nuclear localization of 11E7.
On robust estimation of effect size under semiparametric models

Estimation of effect size is of interest in many applied fields such as Psychology, Sociology and Education. However there are few nonparametric estimators of effect size proposed in the existing literature, and little is known about the distributional characteristics of these estimators. In this article, two estimators based on the sample quantiles are proposed and studied. The first one is the estimator suggested by Hedges and Olkin (see page 93 of Hedges & Olkin, 1985) for the situation where a treatment effect is evaluated against a control group (Case A). A modified version of the robust estimator by Hedges and Olkin is also proposed for the situation where two parallel treatments are compared (Case B). Large sample distributions of both estimators are derived. Their asymptotic relative efficiencies with respect to the normal maximum likelihood estimators under several common distributions are evaluated. The robust properties of the proposed estimators are discussed with respect to the sample-wise breakdown points proposed by Akritas (1991). Simulation studies are provided in which the performing characteristics of the proposed estimator are compared to that of the nonparametric estimators by Kraemer and Andrews (1982). Interval estimation of the effect sizes is also discussed. In an example, interval estimates for the data set in Kraemer and Andrews (1982) are calculated for both cases A and B.
Improved “Optical Highlighter” Probes Derived from Discosoma Red Fluorescent Protein

The tetrameric red fluorescent protein, DsRed, undergoes a rapid red to green color change evoked by short wavelength (λ < 760 nm) femtosecond irradiation—a phenomenon that underpins the application of DsRed as an “optical highlighter” probe for tracking live cells, organelles, and fusion proteins. This color change results from selective bleaching of the “mature” red-emitting species of DsRed and an enhancement of emission from the “immature” green species, likely caused by dequenching of fluorescence resonance energy transfer occurring within the protein tetramer. Here, we have examined the role of residues known to influence the rate and completeness of chromophore maturation on the cellular and biophysical properties of DsRed mutants. Surprisingly, a single amino acid mutation (N42Q) with increased basal green emission yet rapid chromophore maturation displayed a multiphoton-evoked color change that was brighter, more consistent, more vivid, and easier to evoke than DsRed, despite the larger proportion of green chromophores. Rapidly maturing mutants with more complete chromophore maturation, exhibited little color change and increased resistance to multiphoton bleaching. We describe improved optical and cell biological properties for two DsRed-derived variants which we showcase in photolabeling studies, and discuss these data in terms of implications for fluorescence resonance energy transfer-based probes.
Composition of weight loss in morbidly obese patients after gastric bypass.

Abstract Optimal treatment of morbid obesity requires reduction of excess body fat while minimizing lean tissue loss. In order to determine if gastric bypass surgery satisfies both these requirements, we have studied changes in body composition and weight loss in adult (mean age = 33 years) morbidly obese patients (14 males, 68 females) after gastric bypass surgery. The preoperative weight of this cohort was 136 ± 27 (SD) kg, which was 228 ± 37% of ideal body weight by actuarial standards. Lean body mass (LBM) was estimated from potassium-40 measurements obtained from a wholebody potassium-40 counter and by urine creatinine excretion on a subgroup of 20 patients. The average weight loss at 3, 6, and 12 months after surgery was 25, 35, and 46 kg, respectively. The weight loss phase lasted approximately 1 year, at which time 34% of the initial weight was lost and the percentage of loss of excess weight above ideal body weight plateaued at 61%. LBM accounted for 32% of the total weight loss at 1 month, 11% at 6 months, and only 3% at the end of 1 year. The percentage of body weight represented by LBM increased from 35% prior to surgery to 51% by 18 months after gastric bypass. Actual LBM content increased steadily after the first month following surgery. Mean total weight loss following three different surgical procedures for gastric bypass did not differ significantly. Gastric bypass surgery appears to satisfy the objectives of reducing excess weight contributed by fat while minimizing lean tissue loss in morbidly obese patients.
Biosynthesis of Choline-Containing Lipids by Ruminant Mammary Tissue

Abstract Ruminant mammary tissues utilized cytidinediphosphocholine-l,2- 14 C for biosynthesis of the choline-containing lipids, i.e., phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin, which were secreted into milk. Experiments performed both in vivo and in vitro revealed that phosphatidylcholine always attained the highest specific activity. The radioactivity in the phosphatidylcholine fraction decreased rapidly compared to that of the lysophosphatidylcholine and sphingomyelin fractions. The rate of decrease of the specific activity of phosphatidylcholine was consistent with the suggestion that two discrete pools of this compound are present in lactating mammary tissue.
Core Sequence of PAPf39 Amyloid Fibrils and Mechanism of pH-Dependent Fibril Formation: The Role of Monomer Conformation

PAPf39, a 39-residue peptide fragment from human prostatic acidic phosphatase, has been shown to form amyloid fibrils in semen (SEVI), which increase HIV infectivity by up to 5 orders of magnitude. The sequence of the PAPf39 fibrillar core was identified using hydrogen–deuterium exchange (HDX) mass spectrometry and protease protection assays. The central and C-terminal regions are highly protected from HDX and proteolytic cleavage and, thus, are part of the fibrillar core. Conversely, the N-terminal region is unprotected from HDX and proteolytic cleavage, suggesting that it is exposed and not part of the fibrillar core. This finding was tested using two N-terminal truncated variants, PAPf39Δ1–8 and PAPf39Δ1–13. Both variants formed amyloid fibrils at neutral pH. However, these variants showed a markedly different pH dependence of fibril formation versus that of PAPf39. PAPf39 fibrils can form at pH 7.7, but not at pH 5.5 or 2.5, while both N-terminally truncated variants can form fibrils at these pH value...
Use Of Titanium Staples During Upper Tract Laparoscopic Reconstructive Surgery: Initial Experience

ABSTRACTPurpose: Using nonabsorbable titanium staples in the lower urinary tract during laparoscopic nephroureterectomy has been shown to be safe. Laboratory studies of titanium staples in the upper urinary tract have likewise been favorable. Therefore, we used titanium Endo-GIA tissue staples (United States Surgical, Norwalk, Connecticut) to facilitate laparoscopic reduction pelvioplasty during laparoscopic pyeloplasty.Materials and Methods: Of the 17 cases of reduction pelvioplasty closure was done in 12 using absorbable sutures, while in 5 reduction was done with an Endo-GIA stapler. Followup consisted of office visits and telephone interviews plus radionuclide renal scans.Results: Average operative time was 5.5 hours in the Endo-GIA group compared with 6.8 hours in the sutured group. In the latter group extravasation in 2 patients postoperatively was managed conservatively. There was no extravasation in the stapled group. At a median subjective followup of 27 months none of the 5 patients who underwen...
Intermittent Prophylaxis with Oral Truvada Protects Macaques from Rectal SHIV Infection

HIV continues to spread globally, mainly through sexual contact. Despite advances in treatment and care, preventing transmission with vaccines or microbicides has proven difficult. A promising strategy to avoid transmission is prophylactic treatment with antiretroviral drugs before exposure to HIV. Clinical trials evaluating the efficacy of daily treatment with the reverse transcriptase inhibitors tenofovir disoproxil fumarate (TDF) or Truvada (TDF plus emtricitabine) are under way. We hypothesized that intermittent prophylactic treatment with long-acting antiviral drugs would be as effective as daily dosing in blocking the earliest stages of viral replication and preventing mucosal transmission. We tested this hypothesis by intermittently giving prophylactic Truvada to macaque monkeys and then exposing them rectally to simian-human immunodeficiency virus (SHIV) once a week for 14 weeks. A simple regimen with an oral dose of Truvada given 1, 3, or 7 days before exposure followed by a second dose 2 hours after exposure was as protective as daily drug administration, possibly because of the long intracellular persistence of the drugs. In addition, a two-dose regimen initiated 2 hours before or after virus exposure was effective, and full protection was obtained by doubling the Truvada concentration in both doses. We saw no protection if the first dose was delayed until 24 hours after exposure, underscoring the importance of blocking initial replication in the mucosa. Our results show that intermittent prophylactic treatment with an antiviral drug can be highly effective in preventing SHIV infection, with a wide window of protection. They strengthen the possibility of developing feasible, cost-effective strategies to prevent HIV transmission in humans.
Insulin Resistance in Systemic Hypertension: Pharmacotherapeutic Implications

Systemic hypertension, a vascular disease with multiple origins, now is being linked to subtle abnormalities in glucose metabolism, which include insulin resistance and hyperinsulinemia. These conditions often occur together in patients with obesity, noninsulin-dependent diabetes, or both. Hyperinsulinemia and insulin resistance may cause systemic hypertension through multiple mechanisms. Insulin has a salt-retaining effect on the kidney. Also, insulin can augment catecholamine release, increase vascular sensitivity to vasoconstrictor substances, and decrease vascular sensitivity to vasodilator substances. In addition, insulin can increase production of tissue growth factors and help retain sodium and calcium in cells. Insulin resistance in patients can be treated with regular aerobic exercise, weight reduction, and a high-fiber diet. Pharmacologic approaches include hypoglycemic drugs, weight-reducing agents, and certain antihypertensive drugs that may have a favorable impact on both blood pressure and insulin resistance.
BioVision: an application for the automated image analysis of histological sections.

Abstract We describe a computer application, “BioVision”, that can be trained to quickly and effectively classify and quantify user definable histological objects (e.g., senile plaques, neurofibrillary tangles) within single or double-labeled immunocytochemically stained sections. For a given image population, BioVision is interactively trained (in Independent User Mode ) by an investigator to perform the desired classifications. This training yields a statistical model of the different types of objects occurring in the target image population. The resulting model can then be used (in Automated User Mode ) to classify all objects in any image or images from the target population. BioVision simplifies the quantification of complex visual objects and improves inter-rater reliability. The program accomplishes classification in two major stages: pixel classification and blob classification. In pixel classification, each pixel is assigned to one of some number of substance classes, based on its chromatic properties and local context, reflecting basic histological distinctions of interest. In the blob classification phase, the image's pixels are first partitioned into “blobs”: maximal connected sets of pixels assigned to the same substance class. Then, based on its size, shape, textural and contextual properties, each blob is assigned to a histological object class. A Bayesian classifier is used in each of the pixel and blob classification stages. We report several tests of BioVision. First, we applied BioVision to classify senile plaques and neurofibrillary tangles in several test cases of Alzheimer's brain immunostained for beta-amyloid and PHF-tau and compared the results to those produced by experienced investigators. BioVision was trained to classify Plaque-type blobs as either plaques or plaque-type nonentities, and tangle-type blobs as either tangles or tangle-type nonentities. BioVision classified the objects with an accuracy comparable to the trained investigator. Next, we applied BioVision to the task of counting all the tangles in hippocampal images from 22 Alzheimer's disease (AD) cases selected to span a broad range of dementia levels from the tissue repository of UC Irvine's Center for the study of Brain Aging and Dementia. The tangle counts produced by BioVision proved to be significantly better predictors of the cases’ adjusted MMSE scores than any of tangle load, age at death, post mortem interval or the interval between the last MMSE score and death.
A new approach to the demand for public goods

Abstract The individual demand for public goods is measured by a new survey research instrument which permits respondents to make hypothetical expenditure and tax recommendations with moveable penny coupons. Because each respondent faces an identical coupon budget constraint, it may be expected that observed expenditure and tax recommendations represent individual maximum utility. The instrument was applied to a random sample of 1000 residents of North Carolina. Statistical analysis of the resultant data indicates significant socio-economic differences in the preferences for particular spending and tax categories.
The N of 1 trials design in the rheumatic diseases

Recently the N of 1, or single case experimental trial design, has increased in popularity among physicians and therapists interested in assessing the usefulness of a therapeutic modality within a single subject [1, 2]. The techniques are not considered new; single case experimental designs have found acceptance and widespread use for many years in the behavioral sciences [3]. Additionally, experimental physiology and medicine have employed these methods extensively over the last few decades, although there is a relative paucity of articles in the clinical literature that report the results of N of 1 trials. There is a variety of design options possible for N of 1 studies, and the interested reader is referred to Reference 3 for a more comprehensive review of the topic. This paper will review a few of the major design options, with particular attention given to the alternating treatment design (ATD). The advantages and drawbacks of the N of 1 technique, with specific reference to the field of rheumatology, will be the main emphasis.
“Baptists and Bootleggers, Once Removed”: The Politics of Radioactive Waste Internalization in the European Union

This article examines the emergence of an unusual coalition of opponents and proponents of nuclear power, united in their insistence that the EU's high-level radioactive waste (HLW) be disposed of within the EU, and in their opposition to the export of HLW beyond the EU. We argue that this odd coalition is best understood by considering the waste disposal issue within the context of the industry's entire production chain. The activist-industry consensus represents a coalition of “baptists and bootleggers, once removed” brought together not by opposition to HLW exports per se, but rather by the intersection of the issue of radioactive waste disposal with that of nuclear power generation. For quite different reasons, both partners believe that internalizing the EU's radioactive waste is more likely than export to advance their respective goals, be it the expansion or elimination of nuclear power.
Recent B physics results from D0

The D0 detector as collected over 3.7 fb{sup -1} of high quality data. With this large data set, D0 is able to perform a number of precision B lifetime and CP asymmetry measurements. Additionally D0 is measuring a number of properties of B hadrons (B{sub s} and B{sub c}) which are currently only accessible at the Tevatron.
Organization of Serpin Gene-1 from Manduca sexta EVOLUTION OF A FAMILY OF ALTERNATE EXONS ENCODING THE REACTIVE SITE LOOP

Manduca sexta serpin gene-1 encodes a family of serpins whose amino acid sequences are identical in their amino-terminal 336 residues but variable in their carboxyl-terminal 39-46 residues, which includes the reactive site loop (Jiang, H., Wang, Y., and Kanost, M. R. (1994) J. Biol. Chem. 269, 55-58). Here, we report the gene's complete nucleotide sequence and exon-intron structure. A unique characteristic of this gene is its exon 9, which is present in 12 alternate forms between exons 8 and 10. Isolation and characterization of cDNA clones containing exons 9C, 9H, and 9I, which were not found previously, indicate that all 12 alternate forms of exon 9 can be utilized to generate 12 different serpins. The splicing pathway apparently allows inclusion of only one exon 9 per molecule of mature serpin-1 mRNA. Analysis of exon-intron border sequences reveals unique features that may be involved in regulation of RNA splicing. The exon 9 region has apparently evolved through rounds of exon duplication and sequence divergence. The exons near the center of the region may have evolved recently, whereas the outermost exons are the most ancient. Exons 9G and 9H were duplicated as a pair from exons 9E and 9F, an event that may have occurred more than once in the history of this gene.
Electrical taste thresholds established on the medial tongue using two sizes of electrodes.

Objectives/Hypothesis: The present study determined whether a 125 mm2 electrode would produce lower and more reliable electrical taste thresholds than a 25 mm2 electrode when measurement occurred in a medial tongue region relatively sparse in taste bud numbers. We hypothesized this would be the case and that the obtained threshold values would be higher than those previously reported for anterior and lateral tongue regions. Study Design And Methods: Sixteen college-age subjects were tested twice, once using the 25 mm2 electrode and once using the 125 mm2 electrode on each of two sessions separated by 2 to 16 days. The order of presentation of the sessions was counterbalanced across subjects. Measurement was confined to the medial tongue, 0.7 cm lateral to the median furrow. Results: As hypothesized, the larger electrode resulted in lower and more reliable threshold values than the smaller electrode (respective median threshold values = 20.06 μA & 33.59 μA, P = .001; respective test-retest rs = 0.78 [P < .001] and 0.46 [P < .05]). Also as hypothesized, the threshold values were higher (i.e., sensitivity lower) than previously reported for anterior and lateral tongue regions. Conclusions: The magnitude and reliability of electrical taste thresholds depends on the tongue region examined and the size of the electrodes used. These results suggest that relatively large electrodes should be considered for electrogustometric threshold testing, particularly when lingual regions not highly populated with taste buds are evaluated.
Effects of environmental stress or ACTH treatment during pregnancy on maternal and fetal plasma androstenedione in the rat.

Prenatal stress applied during the last trimester of pregnancy has been shown to alter fetal development and influence adult sexual behavior. Since androstenedione (Δ4) has the potential to participate in differentiation processes, this study was designed to assess the effect of prenatal stress on maternal and fetal Δ4 titers. Restraint/illumination/heat (environmental stress) or ACTH injections were used to stress pregnant rat dams beginning on Day 14 of pregnancy. Blood samples and organ weights were obtained from nonpregnant animals, pregnant rats on Days 5, 10, 15, 18, and 20 of pregnancy, and fetuses on Days 18 and 20 of gestation. Maternal and male and female fetal Δ4 titers were determined by radioimmunoassay. ACTH and environmental stress significantly reduced fetal body weight and male anogenital distance. Environmental stress also significantly reduced the size of 20-day fetal adrenals and testes. Each treatment caused significant short-term (1 hr after treatment) and long-term (16 hr after treatment) elevation of maternal plasma Δ4 on Days 15 and 18 of gestation, but only short-term elevation of Δ4 titers on Day 20. ACTH treatment did not cause long-term elevation of fetal Δ4 although both ACTH treatment and environmental stress generated a significant short-term increase in fetal Δ4 titers. Environmental stress produced long-term elevation of fetal Δ4 in 18-day fetuses of both sexes and in 20-day female fetuses. It is concluded that maternal stress and exogenous ACTH significantly elevate maternal and fetal Δ4 titers during the prenatal period postulated to be critical in sexual differentiation of the rat brain.
Case study : corticosteroid treatment of language regression in pervasive developmental disorder

The authors describe a child whose language and behavior regressed at 22 months and in whom pervasive developmental disorder was later diagnosed. At 6 years, he displayed a profound receptive-expressive aphasia accompanied by behavioral disturbances characterized by hyperactivity, impaired social interactions, tantrums, gestural stereotypies, and echolalia. A single-photon emission computed tomography scan and steady-state auditory evoked potentials suggested bitemporal and left frontal pathophysiology. The overall profile resembled Landau-Kleffner syndrome, but no electroencephalographic disturbance was evident. Corticosteroid treatment resulted in amelioration of language abilities and behavior. These findings suggest that the factors underlying language regression in pervasive developmental disorder can, in special circumstances, be amenable to pharmacological treatment.
End‐tidal Carbon Dioxide Monitoring in Emergency Medicine, Part 2: Clinical Applications

End-tidal carbon dioxide (PetCO2) monitoring is becoming more common in both the ED and the out-of-hospital setting. Its main use has been as an aid when confirming endotracheal intubation. Other uses in the ED include monitoring CPR efforts and monitoring the ventilatory and hemodynamic status of intubated and nonintubated patients. In addition, future uses may include using PetCO2 as an adjunct when monitoring the status of asthma treatment, when making the diagnosis of pulmonary embolism, and when measuring cardiac output noninvasively. This article reviews these specific uses of PetCO2 monitoring in emergency medicine.
Real-time analysis of immunogen complex reaction kinetics using surface plasmon resonance

Real-time biospecific interactions of immunogens, measured via BIAcore, were used to verify qualitatively a biosensor design which relies on analyte binding competition reactions to open cross-linked receptor channels. The complexes of importance are: (1) cardiac troponin I (TnI) and monoclonal mouse anti-TnI IgG mAb 265, (2) TnI and bispecific antibodies (BsAbs) which on one end recognize TnI while the other end recognizes nicotinic acetylcholine receptors (nAChRs), (3) nAChRs and rat anti-nAChR IgG mAb 148, (4) nAChRs and BsAbs, (5) nAChRs and Fab'148-TnI biopolymers, and (6) mAb 265 and Fab-TnI biopolymers. A commonly used sensor chip, CM5, was employed to immobilize TnI by covalent amine coupling, while bilayer membrane-associated protein, nAChR, was noncovalently sequestered on a HPA sensor chip via hydrophobic adsorption of membrane lipids. The epitopes of membrane-bound nAChRs were still available to immunogens after being immobilized. Kinetic rate constants and affinities of these systems were calculated from BIAcore sensorgrams. The order of magnitude for dissociation rate constants of the BsAb/TnI linker complex and biopolymer/mAb 265 complex is 10(-2) s-1, which provides an opportunity for competitive binding of free analyte in the sensing systems.
Automatic selection and quantitative analysis of carbides on grain boundaries of 12Kh1MF steel after operation at a steam pipeline of a thermal power plant

A method of computer processing of metallographic images of structures of materials that consists of the automatic (and, at the final stage, interactive) editing of images, localization of analyzed details, and their quantitative analysis is described. As an example, this method was applied to 12Kh1MF low-alloy steel after its operation for ~13⋅104 h at a main steam pipeline of a thermal power plant. We assessed the structures of a straight segment of the steam pipeline and a tension zone of its bend and the integral number and area occupied by carbides located along grain boundaries, using them as indices of degradation of the steel. By using the developed method, we show that the rate of degradation of the steel in the tension zone of the bend is higher than that on the straight segment of the steam pipeline. The metal near the external surfaces of pipes degrades to a larger extent than near the internal surfaces. This is explained by unequal creep resistances of different segments of the steam pipeline in operation.