cssi/SciSciGPT-SciSciNet huggingface dataset:
GPI valence and the fate of secretory membrane proteins in African trypanosomes

Progression of GPI-anchored proteins in bloodstream African trypanosomes correlates with GPI-valence: homodimeric VSG (2 GPI) is a surface protein; heterodimeric transferrin receptor (1 GPI) localizes in the flagellar pocket; homodimeric GPI-minus VSG (0 GPI) is rapidly degraded in the lysosome. We test this relationship using three native secretory/endocytic proteins as monomeric GPI-plus and -minus reporters. GPI-minus procyclin trafficks to the lysosome and is degraded. GPI-plus procyclin trafficks to the flagellar pocket/cell surface and is released (∼50%) with an intact anchor, the remainder (∼50%) is degraded in the lysosome. GPI-plus BiPNHP, derived from the ER marker BiP, is released quantitatively (>80%), while GPI-plus p67HP, derived from the lysosomal marker p67, turns over by both release (∼15%) and lysosomal degradation (>50%). Turnover of endogenous transferrin receptor occurs primarily by lysosomal degradation (>90%). Thus shedding of monovalent GPI reporters correlates inversely with lysosomal targeting. We propose that mono-GPI reporters cycle through the flagellar pocket and endosome until they are disposed of by either shedding or lysosomal targeting. Partitioning between these fates may be a function of individual physical properties. Release is likely due to the exclusive use of C-14:0 myristate in the bloodstream stage GPI anchor. Up-regulation of transferrin receptor by culture in dog serum resulted in prominent cell surface localization, but not in elevated release. Surface receptor was non-functional for ligand binding suggesting that it may be bivalent homodimers of the GPI-anchored ESAG6 receptor subunit.
Recombinant Proteins Can Be Isolated from E. coli Cells by Repeated Cycles of Freezing and Thawing

Repeated cycles of freezing and thawing are sufficient to separate highly expressed recombinant proteins away from the cellular milieu of E. coli. Freezing and thawing liberates recombinant proteins from the bacterial cytoplasm, but does not release the bulk of endogenous E. coli proteins. Furthermore, protein secretion is not required. Fractionation of overexpressed proteins by freeze/thaw treatment does not depend on the identity of the recombinant protein and has been observed for thirty-five different recombinant proteins expressed in E. coli. These include proteins originally found in plant, animal or microbial sources, as well as several proteins designed de novo. Freezing and thawing typically yields approximately 50% of the recombinant protein in relatively pure form. Thus the freeze/thaw treatment can be utilized as a general method for the isolation of recombinant proteins from E. coli.
Chromaticity effects in adaptive optics; wavelength dependence of amplitude compensation

The achievable contrast level for space-based detection of exo-planets will be limited by the stability of the optics. As a consequence, active amplitude and phase compensation will be needed. In order to mitigate these wavefront instabilities, we suggested, as an alternative to classical adaptive optics, the use of a Michelson interferometer equipped with two deformable mirrors. Simulations showed that this set up is able to create a symmetric "dark hole" in an appropriate area of the image plane. However, increasing the bandwidth of the incident light critically alters this nulling performance. A quantitative analysis of this effect will first be presented. An alternative to circumvent this problem is to introduce a dispersive element in one of the legs of the interferometer so that the path length difference does not exhibit the one over wavelength dependence. In the case of the insertion of a gaseous cell, the OPD could then be controlled by pressure variations. The last section of this paper will present a simulation-oriented proof of concept relying on the dispersive properties of nitrogen.
A duality approach to model reference adaptive control and identification

A common framework for model reference adaptive identification and control (MRAI and MRAC) is established. The key idea for this common framework is to maintain the same set of equations for describing the parameterizations of the plant and the model and to solve the control equation properly for each case (identification or control) for the corresponding tuned system, i.e. the model (identification) or the plant (control). Within this framework, two methods, the MOEM (modified output error method) and the IEM (input error method), for the MRAI and MRAC problems are studied, and global asymptotic stability properties are established. >
Constructive Development and Career Transition: Implications for Counseling

The ability to effectively manage career transition may be related to an individual's meaning-making framework, or constructive development. The implications of constructive developmental theory for career choice and implementation are explored. The interplay between career transition and developmental transformation is examined, and counseling strategies for assisting such transformation are proposed. Case illustrations are offered.
Apo2L/TRAIL induction and nuclear translocation of inositol hexakisphosphate kinase 2 during IFN-β-induced apoptosis in ovarian carcinoma

Previously, we have reported that overexpression of IHPK2 (inositol hexakisphosphate kinase 2) sensitized NIH-OVCAR-3 ovarian carcinoma cell lines to the growth-suppressive and apoptotic effects of IFN-β (interferon-β) treatment and γ-irradiation. In the present study, we demonstrate that Apo2L/TRAIL (Apo2L/tumour-necrosis-factor-related apoptosis-inducing ligand) is a critical mediator of IFN-induced apoptosis in these cells. Compared with IFN-α2, IFN-β is a more potent inducer of Apo2L/TRAIL and IHPK2 activity. Overexpression of IHPK2 converts IFN-α2-resistant cells into cells that readily undergo apoptosis in response to IFN-α2. In untreated cells transfected with IHPK2-eGFP (where eGFP stands for enhanced green fluorescent protein), the fusion protein is localized to the cytoplasm and perinuclear region. After treatment with IFN-β, IHPK2-eGFP translocated to the nucleus. In cells transfected with mutant IHPK2-NLS-eGFP (where NLS stands for nuclear localization sequence), containing point mutations in the NLS, the fusion protein remained trapped in the cytoplasm, even after IFN-β treatment. Cells expressing mutant NLS mutation were more resistant to IFN-β. The IC50 value of IHPK2-expressing cells was 2–3-fold lower than vector control. The IC50 value of NLS-mutant-expressing cells was 3-fold higher than vector control. Blocking antibodies to Apo2L/TRAIL or transfection with a dominant negative Apo2L/TRAIL receptor (DR5Δ) inhibited the antiproliferative effects of IFN-β. Thus overexpression of IHPK2 enhanced apoptotic effects of IFN-β, and expression of the NLS mutant conferred resistance to IFN-β. Apo2L/TRAIL expression and nuclear localization of IHPK2 are both required for the induction of apoptosis by IFN-β in ovarian carcinoma.
Tektite compositional trends and experimental vapor fractionation of silicates

Tektite composition considered from results of high temperature vapor fractionation of silicates
Influence of Random Fluctuations in the Λ‐Effect on Meridional Flow and Differential Rotation

We present a mean field model based on the approach taken by Rempel in order to investigate the influence of stochastic fluctuations in the Reynolds stresses on meridional flow and differential rotation. The stochastic fluctuations found in the meridional flow pattern directly resemble the stochastic fluctuations of the Reynolds stresses, while the stochastic fluctuations in the differential rotation are smaller by almost 2 orders of magnitude. It is further found that the correlation length and timescale of the stochastic fluctuations have only a weak influence on meridional flow, but a significant influence on the magnitude of variations in the differential rotation. We analyze the energy fluxes within the model to estimate timescales for the replenishment of differential rotation and meridional flow. We find that the timescale for the replenishment of differential rotation (~10 years) is nearly 4 orders of magnitude longer than the timescale for the replenishment of meridional flow, which explains the differences in the response to stochastic fluctuations of the Reynolds stress found for both flow fields.
The impact of collectivism on savings behavior: a case study of Mexican-Americans and non-Mexican Latinos

This interdisciplinary study combines anthropological and economic theories and methods to understand how Mexican-Americans’ collectivist cultural values affect their savings behavior and their preparation for retirement. Mexican-Americans are the fastest growing immigrant group in the United States and they are both younger and expected to live longer than other groups. Yet they are the most insecure in relation to funding retirement. Even when Mexican-American workers are eligible to participate in retirement savings plans at work, they have low participation rates. We analyze data from a Chicago area survey in light of broader anthropological and economic scholarship to argue that Mexican-Americans’ collectivist values influence the choices they make about how to build assets and resources differently from other Latino groups. Latinos are a diverse group by national origin, citizenship and immigration status, characteristics that strongly influence their employment prospects, asset building and retirement savings and security. Financial policy makers need to understand the heterogeneity of financial behavior within the Hispanic community. The collectivist informal economy of Mexican immigrants and their children is at odds with the formal defined contribution retirement savings system, which is geared toward both autonomous individuals and higher-income workers who benefit from the program’s tax deductions. Since these plans penalize participants who withdraw funds before retirement age, they can be deleterious to those who expect both to loan funds to and to borrow money from members of their collectivist social networks.
Modelling solar radiation over complex terrains using monthly climatological data

Meteorological stations placed in remote areas (such as mountainous sites) often record only precipitation and air temperature data, summarised into monthly tables. There is therefore a need for appropriate methods to estimate solar radiation data from monthly inputs. It is important to know the quality and characteristics of the estimates made in order to understand what impacts the modelled data may have on the use to which they are meant. This paper evaluates the behaviour of two empirical models based on the difference between maximum and minimum air temperatures and compares results with a newly developed model, for 24 stations (11 for model calibration, the rest for model validation) in Italian sites. The new model (SRMCT, solar radiation model for complex terrains) replaces the minimum air temperature with a monthly function and uses rainy days number to correct the air temperature range. Comparisons were made using a fuzzy-logic-based multiple-statistics assessment approach (Irad). An appraisal of the temporal distribution of mean errors over a year was also performed. The new model produced the best overall estimates. The two air temperature-based models can be an alternative approach when only air temperature data are available, but at many sites they introduced large inaccuracies and seasonal patterns in the error distribution. The study demonstrates the appropriateness of both air temperature range and rain correction factors for monthly based solar radiation estimates. At the same time, it shows the value and importance of using a range of assessment statistics, even aggregated into an overall indicator, to evaluate model estimates.
Effects of "below-zero" habituation on spontaneous recovery and dishabituation of the orienting response.

Twenty male undergraduate Ss underwent habituation of the skin conductance component of the orienting response to a neutral tone, spontaneous recovery, rehabituation, and dishabituation (habituation, H condition). Another 20 Ss underwent the same procedure, except they received an additional 10 stimulus presentations immediately after initial habituation (extended habituation, EH condition). The EH condition resulted in more (not significant) spontaneous recovery and trials to rehabituation than did the H condition, indicating that such a “below-zero” habituation procedure did not strengthen habituation. There were significant differences between the groups in response to a post-rehabituation buzzer (dishabituating stimulus), and in response to the subsequent re-presentation of the original tone stimulus (dishabituation), the EH group giving larger responses than the H group. These latter results were seen as consonant with both the Sokolov (1963) and Groves and Thompson (1970) approaches to habituation, and were discussed in that context.
Pain related to cancer treatment

Pancreatic cancer patients experience painful diagnostic and therapeutic events in addition to the pain of the disease. Such discomforts, though nontrivial, are often ignored by caregivers because pain of iatrogenic origin is typically overshadowed by the severe and relentless pain of the tumor. Below, the basic mechanisms of iatrogenic pain are reviewed and several potentially painful events and complications affecting pancreatic carcinoma patients are considered. Several new developments in patient self-administered palliative care are also described. These hold promise for improving the management of both iatrogenically induced pain and residual (postceliac plexus block) pain in this population of patients.
Monte Carlo study of very weakly first-order transitions in the three-dimensional Ashkin-Teller model

Abstract We propose numerical simulations of the Ashkin-Teller model as a foil for theoretical techniques for studying very weakly first-order phase transitions in three dimensions. The Ashkin-Teller model is a simple two-spin model whose parameters can be adjusted so that it has an arbitrarily weakly first-order phase transition. In this limit, there are quantities characterizing the first-order transition which are universal: we measure the relative discontinuity of the specific heat, the correlation length, and the susceptibility across the transition by Monte Carlo simulation.
Reactions of nitriles at semiconductor surfaces

Motivated by the recent interest in using nitriles for organic modification of semiconductor surfaces, we have used density functional theory and cluster models to study the reactions of nitriles on semiconductor surfaces. In particular, we have calculated the energetics for the surface reactions of acetonitrile, 2-propenenitrile, and 3-butenenitrile on the Si(100)-2 x 1 and Ge(100)-2 x 1 surfaces. For acetonitrile, our calculations predict that although it forms multiple products on the Si(100)-2 x 1 surface, the molecule does not react on the Ge(100)-2 × 1 surface. For 2-propenenitrile, the calculations show that whereas the C=C [2 + 2] cycloaddition product is thermodynamically most stable, formation of the hetero-[4 + 2] product is kinetically favored. We also have investigated the possibility of surface-catalyzed isomerization of 3-butenenitrile to 2-butenenitrile on the Si(100)-2 x 1 and Ge(100)-2 x 1 surface. We find that there are multiple surface-catalyzed isomerization pathways on the Si(100)-2 x 1 and Ge(100)-2 x 1 surfaces. However, our calculated kinetics predicts that the amount of 2-butenenitrile formed by surface-catalyzed isomerization is small.
Early genetic amniocentesis and its relationship to respiratory difficulties in paediatric patients: A report of findings in patients and matched controls 3–5 years post‐procedure

This study evaluates the long-term pulmonary complications of 25 children from a prospective, matched-control, pilot study evaluating short-term complications of early (11-14 weeks' gestation) versus traditional (15 weeks' gestation and later) genetic amniocentesis. Five children in the early amniocentesis group were found to have various respiratory difficulties, a morbidity rate comparable to that of paediatric patients in the general population. These data identify the need for larger, multicentre trials.
A prospective study of the impact of helmet usage on motorcycle trauma.

STUDY OBJECTIVE: To determine the effect of the use of a motorcycle helmet on reducing the mortality, morbidity, and health care costs resulting from motorcycle crashes. DESIGN: A prospective, multicenter study of all eligible motorcycle crash victims. SETTING: The emergency departments of eight medical centers across the state of Illinois, including representatives from urban, rural, teaching, and community facilities. TYPE OF PARTICIPANTS: All motorcycle crash victims presenting less than 24 hours after injury for whom helmet information was known. Data were collected from April 1 through October 31, 1988. MEASUREMENTS AND MAIN RESULTS: Fifty-eight of 398 patients (14.6%) were helmeted, and 340 (85.4%) were not. The nonhelmeted patients had higher Injury Severity Scores (11.9 vs 7.02), sustained head/neck injuries more frequently (41.7 vs 24.1%), and had lower Glasgow Coma Scores (13.73 vs 14.51). Twenty-five of the 26 fatalities were nonhelmeted patients. By logistic regression, the lack of helmet use was found to be a major risk factor for increased severity of injury. A 23% increase in health care costs was demonstrated for nonhelmeted patients (average charges $7,208 vs $5,852). CONCLUSION: Helmet use may reduce the overall severity of injury and the incidence of head injuries resulting from motorcycle crashes. A trend toward higher health care costs was demonstrated in the nonhelmeted patients.
The collection of terrestrial slugs (Gastropoda: Pulmonata) at the Museum of Natural History, Wrocław University (Poland)

The collection of terrestrial slugs of the Museum of Natural History, Wroc3aw University, comprises 69 descriptive types as well as material representing 172 species mainly from the Northern Hemisphere.
A kinetic ESR study of the reaction of t-butylperoxy radicals with hexaphenylditin and hexaphenyldilead☆

Abstract Absolute rate constants for the reaction of t-butylperoxy radicals with hexaphenylditin and hexaphenyldilead have been found to fit the equations log ( k p / M −1 ·s −1 ) = (5.5±0.15) − (3800±150)/Θ and log ( k p / M −1 ·s −1 ) (9.5±0.3) − (6000±250)/Θ, where Θ = 2.303 RT cal mol −1 , respectively.
Inappropriate and Excessive Guilt: Instrument Validation and Developmental Differences in Relation to Depression.

Inappropriate or excessive guilt is listed as a symptom of depression by the American Psychiatric Association (1994). Although many measures of guilt have been developed, definitional and operational problems exist, especially in the application of such measures in childhood and adolescence. To address these problems, the current study introduces the Inappropriate and Excessive Guilt Scale (IEGS), assesses its validity for use with children and adolescents, and tests its relation to depression across development. From a sample of 370 children between 7 and 16 years old, results provided (1) evidence that items designed to assess inappropriate and excessive guilt converged onto a single underlying factor, (2) support for the convergent, discriminant, and construct validity of the IEGS in a general youth population, and (3) evidence of incremental validity of the IEGS over-and-above other measures of guilt. Results also supported the hypothesis that inappropriate and excessive guilt as well as negative cognitive errors become less normative and more depressotypic with age.
Real-Time Analysis of Methanol in Air and Water by Membrane Introduction Mass Spectrometry

We present results for the near-real-time, on-line detection of methanol in both air and water using membrane introduction mass spectrometry (MIMS). In these experiments, we compare the sensitivity of a poly(dimethylsiloxane) (PDMS) membrane and an allyl alcohol (AA) membrane to the detection of methanol. In MIMS, the membrane serves as the interface between the sample and the vacuum of the mass spectrometer. Membrane-diffused water was used as the reagent ion (H3O+) for chemical ionization of methanol in an ion trap mass spectrometer. Linear calibration curves have been obtained for methanol using both PDMS and AA membranes. For PDMS, detection limits of methanol are 14 ppmv and 5 ppm in air and water, respectively. For AA, detection limits are 3.3 ppmv and 2 ppm in air and water, respectively. We demonstrate that the sensitivity of the analysis can be altered by the chemistry of the membrane. When the AA membrane is used, the sensitivity of MIMS is enhanced over that of PDMS by a factor of 8.5 for metha...
Response of sensory neurites and growth cones to patterned substrata of laminin and fibronectin in vitro

During neurite elongation in the developing peripheral nervous system, the distribution of laminin and fibronectin may provide preferred substrates for neurite elongation. In this study, the response of sensory neurites and growth cones to patterns of laminin or fibronectin applied to a background substrate of Type IV collagen was studied to determine any possible substrate preference. Neurites exhibited elongation restricted to a laminin pattern, but not a fibronectin pattern, indicating that sensory neurites prefer to elongate on laminin compared to Type IV collagen. When polylysine is included in the background substrate, neurite preference for laminin is decreased. Laminin also enhances neurite elongation and defasciculation and stabilizes growth cone protrusions. These results suggest an adhesive as well as a cytoskeletal involvement in the response to laminin, but direct adhesion estimates indicate that laminin decreases overall adhesion, arguing against an adhesive involvement. Regardless of the mechanism involved, the observed neurite preference for laminin is consistent with the hypothesis that spatial and temporal laminin distributions provide preferred pathways for peripheral neurite elongation.
Estimation of Parameters of the Generalized Geometric Distribution Using Ranked Set Sampling

The estimates of the parameters of the generalized geometric distribution are obtained by using ranked set sampling procedure. These estimates are compared with the ordered least squares estimates given by Downton (1954, Annals of Mathematical Statistics 25, 303-316). It is shown that the relative precisions of our estimators are higher than those of the ordered least squares estimators. Furthermore, the relative precision of our estimator for the population mean is higher than the usual estimator based on ranked set sampling.
Clostridium perfringens growth from spore inocula in sous-vide processed pork-based Mexican entrée.

The combined effect of Citricidal wih irradiation on Clostridium perfringens growth from spores in a sous-vide processed marinated pork meat Mexican entree was investigated. Citricidal was added at 200 or 800 ppm after mixing pork meat with tomatillo sauce and inoculated with 3 log(10) CFU/g of C. perfringens spores. Samples were irradiated at either 0 or 2 kGy, heated to an internal temperature of 71 degrees C, and stored at 4 degrees C for 28 d, 15 degrees C for 45 d, and 25 degrees C for 26 h. To simulate the conditions that may occur during transportation, distribution, storage, or handling in supermarkets or by consumers, the effect of static temperature abuse on C. perfringens growth was assessed by transferring samples stored at 4 to 25 degrees C for 13 and 15 h. Total C. perfringens populations were determined by plating diluted samples on tryptose-sulfite-cycloserine agar. Growth was not observed up to 45 d of storage at 15 degrees C in samples supplemented with 800 ppm of Citricidal. At 25 degrees C, no significant differences (P > 0.05) on the lag phase duration due to antimicrobial treatments was observed. The temperature abuse of refrigerated products for up to 15 h did not lead to C. perfringens growth to high infective dose levels of 1 million cells required to cause food poisoning. The results suggest that 800 ppm Citricidal can have significant bacteriostatic activity against C. perfringens and may provide a degree of protection against this pathogen in sous-vide processed marinated pork meat Mexican entree, under mild temperature abuse (<or= 15 degrees C) conditions.
Phosphodiesterase 5 Inhibition Attenuates Cerebral Vasospasm and Improves Functional Recovery After Experimental Subarachnoid Hemorrhage

Background Cerebral vasospasm is an independent predictor of poor outcome after subarachnoid hemorrhage (SAH). The nitric oxide-cyclic guanosine monophosphate (NO-cGMP) vasodilatory pathway is strongly implicated in its pathophysiology. Preliminary studies suggest that phosphodiesterase 5 (PDE5), an enzyme that degrades cGMP, may play a role because the PDE5 inhibitor sildenafil was found to reduce vasospasm after SAH. However, several questions that are critical when considering translational studies remain unanswered. Objective To elucidate the mechanism of action of sildenafil against vasospasm and to assess whether sildenafil attenuates SAH-induced neuronal cell death, improves functional outcome after SAH, or causes significant physiological side effects when administered at therapeutically relevant doses. Methods SAH was induced via endovascular perforation in male C57BL6 mice. Beginning 2 hours later, mice received sildenafil citrate (0.7, 2 or 5 mg/kg orally twice daily) or vehicle. Neurological outcome was assessed daily. Vasospasm was determined on post-SAH day 3. Brain PDE5 expression and activity, cGMP content, neuronal cell death, arterial blood pressure, and intracranial pressure were examined. Results We found that PDE5 activity (but not expression) is increased after SAH, leading to decreased cGMP levels. Sildenafil attenuates this increase in PDE5 activity and restores cGMP levels after SAH. Post-SAH initiation of sildenafil was found to decrease vasospasm and neuronal cell death and markedly improve neurological outcome without causing significant physiological side effects. Conclusion Sildenafil, a US Food and Drug Administration-approved drug with a proven track record of safety in humans, is a promising new therapy for vasospasm and neurological deficits after SAH.
Endocrine Health Problems Detected in 519 Patients Evaluated in a Pediatric Cancer Survivor Program

Context: Many pediatric cancer survivors have endocrine conditions. Surveillance for late effects is recommended by national guidelines. Endocrine surveillance is recommended after alkylating agents, steroids, methotrexate, and radiation. Objective: The objective of the study was to describe the endocrine outcomes in patients followed up in a program that uses national screening guidelines. Design: The design of the study was a medical records review. Setting: The study was conducted in the Comprehensive Cancer Survivor Program, an academic pediatric oncology program. Participants: The study included 519 pediatric and young adult survivors of noncentral nervous system childhood malignancies between January 1, 2001, and December 15, 2005. Intervention: Patients were evaluated with history, physical examinations, and evaluations recommended in the Children's Oncology Group's Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers. Outcome Measures: The frequency and typ...
ANTIMICROBIAL MECHANISMS OF BUTYLATED HYDROXYANISOLE AGAINST TWO Pseudomonas SPECIES

Exposure of Pseudomonas fluorescens and Pseudomonas fragi cells to butylated hydroxyanisole (BHA) resulted in a rapid loss of UV absorbing material and previously incorporated 14C-labeled compounds from the cells. Pseudomonas fluorescens lost a maximum of 15.3% of the incorporated 14C-label when incubated with 200 ppm BHA and 8.0% when incubated with 100 ppm BHA. Pseudomonas fragi was more resistant to BHA losing only 6.4% of the label at 200 ppm and 2.1% at 100 ppm. It was determined that lethality was at least partially due to leakage. The relative percentages of phospho-lipids in P. fragi and major fatty acids in both P. fragi and P. fluorescens were altered by growth in the presence of various concentrations of BHA.
One to one mappings and applications

Abstract This paper is a survey of a number of recent results concerning conditions under which certain 1-1 continuous mappings are homeomorphisms. We also discuss some applications of the theorems on 1-1 mappings, notably how they imply compactness or openness for certain mappings.
Heart period variability and depressive symptoms : Gender differences

Abstract Background: Deceased heart period variability has been associated with cardiac events and depressive symptoms; however, the results of studies are not unequivocal. We hypothesize that gender differences in the various study samples may have contributed to the lack of uniformity of findings. Methods: Time and frequency domain measures of heart period variability during a 5-min resting baseline were examined in 15 depressed (8 female) and 11 nondepressed (6 female) college students. Results: Both time and frequency domain measures indicated an interaction between gender and depressive symptoms, such that depressed male subjects showed less heart period variability, whereas depressed female subjects showed more heart period variability compared to their nondepressed counterparts. Conclusions: These results suggest that future studies investigating the relationship between heart period variability and depressive symptoms examine gender differences.
Topical vaginal drug delivery in the guinea pig. I. Effect of estrous cycle on the vaginal membrane permeability of vidarabine

Summary In previous studies, permeability was shown to be one of the most important factors influencing the delivery of vidarabine and its 5’-O-esters in the vaginal membrane of the mouse. The present report describes the results of the extension of these studies to the guinea pig vaginal membrane. By a vaginal smear procedure, the estrous cycle (approx. 16 days in duration) was monitored by dividing it into five stages. The vaginal membrane permeability of vidarabine was measured during each stage in a two-chamber diffusion cell. This study revealed that the permeability coefficients for vidarabine were 5-100 times higher during the early diestrus stage than during the estrus stage. Additional permeation studies on membranes at the estrus stage were performed by separating the upper layer (keratin layer combined with mucous layer) from the rest of the membrane. The low permeability coefficient of vidarabine for the upper layer suggests that this layer may be the major diffusion barrier (mainly keratin layer) for vidarabine when the drug is topically applied during the estrus stage. The immature guinea pig vaginal membranes showed permeability coefficients comparable to those values obtained from the membranes of mature guinea pigs during the early diestrus stage.
Long-term weight control study. VII (weeks 0 to 210). Serum lipid changes.

We analyzed serum total cholesterol, triglycerides, and lipoprotein profile changes occurring in the participants (N = 121) through 210 weeks of the study. On average, baseline lipid levels were within normal limits. The most consistent changes occurred in the high-density lipoprotein cholesterol (HDL-C), serum total cholesterol/HDL-C ratios, and triglyceride levels. HDL-C increased significantly (p < 0.01), compared with baseline, by 10% at week 34, 15% at week 54, 19% at week 104, and 27% at week 139. At week 210, 20 weeks after treatment had ended, HDL-C was 15% higher than baseline. At weeks 34, 54, 104, and 139, the serum total cholesterol/HDL-C ratio was significantly decreased, compared with baseline, by 9%, 19%, 17%, and 25%, respectively. At week 210, serum total cholesterol/HDL-C ratio was 8% less than week 0. Compared with baseline, triglyceride levels decreased significantly by 21%, 31%, 29%, and 29% at weeks 34, 54, 104, and 139, respectively. At week 210, triglyceride levels were 16% below baseline. Total cholesterol levels and low-density lipoprotein cholesterol (LDL-C) showed less dramatic changes. Patterns of lipid and lipoprotein changes were qualitatively similar between men and women. However, greater decreases in serum total cholesterol, LDL-C, and triglyceride levels were observed in participants with high (n = 10) compared with low (n = 10) baseline lipid levels. Cholesterol changes were not affected by anorexiant medications. However, triglyceride levels at week 34 were significantly (p < 0.025) less in the participants treated with anorexiants. Overall, participants in the long-term weight control study had beneficial changes in their lipid profiles, thus decreasing their risk of coronary heart disease. Clinical Pharmacology and Therapeutics (1992) 51, 634–641; doi:10.1038/clpt.1992.75
Unexpectedly Fast Cis/Trans Isomerization of Xaa-Pro Peptide Bonds in Disulfide-Constrained Cyclic Peptides

Acyclic dithiol and cyclic disulfide forms of the peptides Ac-Cys-Pro-Xaa-Cys-NH2 (Xaa = Phe, His, Tyr, Gly, and Thr) and Ac-Cys-Gly-Pro-Cys-NH2 and the peptide Ac-Ala-Gly-Pro-Ala-NH2 were synthesized and characterized by mass spectrometry and NMR spectroscopy. Rate constants kct and ktc for cis-to-trans and trans-to-cis isomerization, respectively, across the Cys-Pro or Gly-Pro peptide bonds were determined by magnetization transfer NMR techniques over a range of temperatures, and activation parameters were derived from the temperature dependence of the rate constants. It was found that constraints imposed by the disulfide bond confer an unexpected rate enhancement for cis/trans isomerization, ranging from a factor of 2 to 13. It is proposed that the rate enhancements are a result of an intramolecular catalysis mechanism in which the NH proton of the Pro-Xaa peptide bond hydrogen bonds to the proline nitrogen in the transition state. The peptides Ac-Cys-Pro-Xaa-Cys-NH2 and Ac-Cys-Gly-Pro-Cys-NH2 are mode...
A Study of Deproteinization Methods for Subsequent Serum Analysis with Capillary Electrophoresis

Fifteen different methods of serum protein removal are examined for applicability with subsequent serum analysis for low molecular mass metabolites and pharmaceutical agents by capillary electrophoresis (CE). Each of the deproteinization methods considered here has been reported in the literature and successfully used for serum protein removal in other applications. Two of the methods are found to be superior to the others for CE analysis. Protein removal by ultrafiltration with Centrifree Micropartition System filters and by precipitation using acetonitrile worked well for protein removal, as evidenced by reproducible (RSD <6%) determinations of several low molecular weight components. The former is capable of analyzing for free metabolites only, while the latter was found to be somewhat problematic with respect to evaporation of the acetonitrile, causing potential problems with reproducibility. Both techniques for protein removal were clearly suitable for the subsequent serum analysis by CE in untreated fused silica capillaries.
Matrix stiffening sensitizes epithelial cells to EGF and enables the loss of contact inhibition of proliferation

Anchorage to a compliant extracellular matrix (ECM) and contact with neighboring cells impose important constraints on the proliferation of epithelial cells. How anchorage and contact dependence are inter-related and how cells weigh these adhesive cues alongside soluble growth factors to make a net cell cycle decision remain unclear. Here, we show that a moderate 4.5-fold stiffening of the matrix reduces the threshold amount of epidermal growth factor (EGF) needed to over-ride contact inhibition by over 100-fold. At EGF doses in the range of the dissociation constant (Kd) for ligand binding, epithelial cells on soft matrices are contact inhibited with DNA synthesis restricted to the periphery of cell clusters. By contrast, on stiff substrates, even EGF doses at sub-Kd levels over-ride contact inhibition, leading to proliferation throughout the cluster. Thus, matrix stiffening significantly sensitizes cells to EGF, enabling contact-independent spatially uniform proliferation. Contact inhibition on soft substrates requires E-cadherin, and the loss of contact inhibition upon matrix stiffening is accompanied by the disruption of cell–cell contacts, changes in the localization of the EGF receptor and ZO-1, and selective attenuation of ERK, but not Akt, signaling. We propose a quantitative framework for the epigenetic priming (via ECM stiffening) of a classical oncogenic pathway (EGF) with implications for the regulation of tissue growth during morphogenesis and cancer progression.
Neck muscle paths and moment arms are significantly affected by wrapping surface parameters.

In this paper, we studied the effects of wrapping surfaces on muscle paths and moment arms of the neck muscle, semispinalis capitis. Sensitivities to wrapping surface size and the kinematic linkage to vertebral segments were evaluated. Kinematic linkage, but not radius, significantly affected the accuracy of model muscle paths compared to centroid paths from images. Both radius and linkage affected the moment arm significantly. Wrapping surfaces that provided the best match to centroid paths over a range of postures had consistent moment arms. For some wrapping surfaces with poor matches to the centroid path, a kinematic method (tendon excursion) predicted flexion moment arms in certain postures, whereas geometric method (distance to instant centre) predicted extension. This occurred because the muscle lengthened as it wrapped around the surface. This study highlights the sensitivity of moment arms to wrapping surface parameters and the importance of including multiple postures when evaluating muscle path...
Refinement of the primary hydration shell model for molecular dynamics simulations of large proteins

A realistic representation of water molecules is important in molecular dynamics simulation of proteins. However, the standard method of solvating biomolecules, i.e. immersing them in a box of water with periodic boundary conditions, is computationally expensive. The primary hydration shell (PHS) method, developed more than a decade ago and implemented in CHARMM, uses only a thin shell of water around the system of interest, and so greatly reduces the computational cost of simulations. Applying the PHS method, especially to larger proteins, revealed that further optimization and a partial reworking was required and here we present several improvements to its performance. The model is applied to systems with different sizes, and both water and protein behaviors are compared with those observed in standard simulations with periodic boundary conditions and, in some cases, with experimental data. The advantages of the modified PHS method over its original implementation are clearly apparent when it is applied to simulating the 82 KD protein Malate Synthase G.
Inhibition of Prostate Tumor Cell Hyaluronan Synthesis Impairs Subcutaneous Growth and Vascularization in Immunocompromised Mice

Hyaluronan (HA), a secreted glycosaminoglycan component of extracellular matrices, is critical for cellular proliferation and motility during development. However, elevated circulating and cell-associated levels correlate with various types of cancer, including prostate. We have previously shown that aggressive PC3M-LN4 prostate tumor cells synthesize excessive HA relative to less aggressive cells, and express correspondingly higher levels of the HA biosynthetic enzymes HAS2 and HAS3. Inhibition of these enzymes by stable transfection of PC3M-LN4 cells with anti-sense HAS2 or HAS3 expression constructs diminishes HA synthesis and surface retention. In this report, we used these HA-deficient cell lines to examine the role of HA in tumorigenicity. Subcutaneous injection of SCID mice with hyaluronan synthase (HAS) antisense-transfected cells produced tumors threefold to fourfold smaller than control transfectants. Tumors from HAS antisense transfectants were histologically HA-deficient relative to controls. HA deficiency corresponded to threefold reduced cell numbers per tumor, but comparable numbers of apoptotic and proliferative cells. Percentages of apoptotic cells in cultured transfectants were identical to those of control cells, but antisense inhibition of HA synthesis effected slower growth rate of cells in culture. Quantification of blood vessel density within tumor sections revealed 70 to 80% diminished vascularity of HAS antisense tumors. Collectively, the results suggest HAS overexpression by prostate tumor cells may facilitate their growth and proliferation in a complex environment by enhancing intrinsic cell growth rates and promoting angiogenesis. Furthermore, this is the first report of a role for inhibition of HA synthesis in reducing tumor growth kinetics.
Does misery love company? exploring the therapeutic effects of TV viewing on regretted experiences

Testing hypotheses derived from regret and mood management theories, this research explores how regretted experiences impact interest in viewing experience-relevant TV programming and such viewing’s effects on program enjoyment and felt regret. One hundred and forty-four participants, half of whom had been unfaithful in romantic relationships, were asked first to rate their interest in viewing a series of storylines and then to provide their reactions to 1 of 2 versions of a TV program depicting cheating behavior. Largely consistent with hypotheses, results indicated that those who had both cheated and felt regret about their behavior were more likely than others to want to watch experience-related storylines, were no less likely to enjoy watching such programming, and particularly preferred viewing the program version in which the main character rationalized, rather than expressed regret for, her behavior. Both program versions, however, reduced regret equally. A survey of 206 city residents also offered evidence consistent with predictions based on regret theory. Overall, this research speaks to the value of integrating theories of emotion with media theory to enhance the latter’s predictive ability.
Design and fabrication of silicon-based optofluidic waveguide platforms

Using silicon based microfabrication and materials we have developed a photonic platform capable of single bioparticle analysis. This platform combines liquid and hollow core waveguides on the micron-scale (5 μm x 12 μm) to isolate femtoliter sized sample volumes. Fluorescence excitation and signals in the visible range are directed into and out of the sample volume at an orthogonal angle to maximize signal-to-noise. This paper reveals the development path of these structures over several device generations including innovations in material, geometries, and fabrication techniques to increase detection sensitivity.
Preliminary investigations of Monte Carlo simulations of neutron energy and let spectra for fast neutron therapy facilities

Abstract No fast neutron therapy facility has been built with optimized beam quality based on a thorough understanding of the neutron spectrum and its resulting biological effectiveness. A study has been initiated to provide the information necessary for such an optimization. Monte Carlo studies will be used to simulate neutron energy spectra and LET spectra. These studies will be bench-marked with data taken at existing fast neutron therapy facilities. Results will also be compared with radiobiological studies to further support beam quality optimization. These simulations, anchored by this data, will then be used to determine what parameters might be optimized to take full advantage of the unique LET properties of fast neutron beams. This paper will present preliminary work in generating energy and LET spectra for the Fermilab fast neutron therapy facility.
Mechanisms and limits of contrast in optical imaging of cancer

discussed. Some cancers develop as cellular masses which displace normal fibrous tissue or stroma,yielding a net drop in scattering properties. Some cancer may be more fibrous than normal tissuesyielding a net increase in scattering. Cancers sometimes develop increased vascularity which yields anet increase in absorption. Another measure is fluorescence, either autofluorescence or dye-enhancedfluorescence. This paper considers the limits of resolution when optically characterizing a smallspherical object within a turbid tissue. The ability to discriminate a small object with a stronglyincreased absorption vs a larger object with a slight increase in absorption is tested, using frequency-domain light transport with 3-GHz modulation of the light source. The results suggest that an objectabouty 1/10 the size of the tissue within which it is embedded can be distinguished by a pair of
The Relationship Between Hyperinsulinemia And Weight Loss In Black Obese Women

Abstract Obesity is a health problem of considerable magnitude. Ninety-four black obese women currently participating in a lifestyle intervention study were used to determine what relationship exists between hyperinsulinemia (determined at baseline) and change in body mass index (BMI) (at 16 weeks) controlling for the variables: baseline BMI, treatment group, and physical activity level. The subjects were divided into two groups based on baseline fasting serum insulin levels, (normoinsulinemic ⩽ 25 μU/ml and hyperinsulinemic > 25 μU/ml), and a regression analysis was used to determine what relationship exists between fasting serum insulin level and change in BMI. The regression analysis found that baseline fasting serum insulin level was not significantly related to the mean change in log of BMI (t = 0.415, p > 0.05) controlling for the variables: log of BMI at baseline, treatment group, and physical activity level. The analysis did find that the entire regression model (log of BMI at baseline, treatment group, physical activity level, and insulin level) explained 90% of the variation in the mean change in log of BMI (p
Thermal decomposition of arsine on GaAs( 100)

Abstract The thermal dissociation pathways of AsH 3 on Ga-rich (4 × 6) and As-rich c(2 × 8) GaAs(100) surfaces have been studied with high-resolution electron energy loss (HREELS), X-ray photoelectron (XPS) and thermal desorption spectroscopy (TDS). Arsine adsorbs molecularly at 115 K and, based on XPS data, the saturation coverage is 0.16 ± 0.04 ML. In TDS, desorption of the parent molecule is accompanied by As-H bond dissociation starting at temperatures as low as 140 K. Of the resulting AsH x ( x = 1, 2) and H, part recombines to liberate arsine but approximately 15% of the initial AsH 3 coverage dissociates irreversibly resulting in As deposition on the GaAs surface. While on the As-rich surface there is no evidence for Ga-H formation, we do observe transfer of hydrogen from As to Ga sites on the Ga-rich surface. Recombinative hydrogen desorption from Ga-H occurs around 500 K on Ga-rich surfaces, whereas H 2 desorbs at higher temperatures (~ 550 K) from As-H on As-rich surfaces. With regard to atomic layer epitaxy (ALE) of GaAs, these results imply that, in the final stages of an As cycle, removal of hydrogen from As sites limits the rate whereas in the initial stages, Ga-H is the reaction intermediate.
The relationship between pharmacy practice setting and job design.

The context in which pharmacists work has changed over the history of the profession from a majority working as independent shopkee ers to the present situation in which an increasmgly larger num g er of pharmacists work as employees in a variety of work settings. This study examines differences in the cffectiveness of work design within these work settings. A nationwide survey was conducted to dctermine differences between independent, hospital and chain pharmacy settings. Significant differences were observed for aspects of job satisfaction, jobiorganization involvement, turnover, and professionalism. Evidence is presented for recognition of a need for a differentiated job design for practicing pharmacists.