cssi/SciSciGPT-SciSciNet huggingface dataset:
Androgen Receptor Splice Variants are Resistant to Inhibitors of Hsp90 and FKBP52, which alter Androgen Receptor Activity and Expression

Androgen ablation therapy is the most common treatment for advanced prostate cancer (PCa), but most patients will develop castration-resistant prostate cancer (CRPC), which has no cure. CRPC is androgen-depletion resistant but androgen receptor (AR) dependent. AR is a nuclear receptor whose transcriptional activity is regulated by hormone binding to the ligand-binding domain (LBD). Constitutively active AR splice variants that lack LBDs often are expressed in CRPC. The expression of these variants indicates that methods to inhibit AR activity that do not rely on inactivating the LBD are needed. Heat shock protein 90 (Hsp90), a potential therapeutic target in PCa, is an AR chaperone crucial for proper folding, hormone binding and transcriptional activity of AR. We generated LNCaP cell lines with regulated expression of the AR-V7 variant as well as a cell line expressing artificially truncated AR (termed AR-NTD) to characterize splice variant function. Using an Hsp90 inhibitor, Geldanamycin (GA), and an AR-Hsp90-FKBP52 specific inhibitor, MJC13, we sought to determine if the AR variants also require Hsp90 and associated co-chaperone, FKBP52, for their activity. GA inhibits AR transcriptional activity but has little effect on AR-V7 activity. Moreover, GA decreases the stability of AR protein, with no effect on AR-V7 levels. Full-length AR activity is strongly inhibited by MJC13 while AR-V7 is unaffected. Thus, the variants are resistant to inhibitors of the Hsp90-AR heterocomplex. Although Hsp90 inhibitors will continue to inhibit growth promoting kinases and signaling through activated full-length AR in CRPC, AR signaling through variants will be retained.
The Activated Insulin-Like Growth Factor I Receptor Induces Depolarization in Breast Epithelial Cells Characterized by Actin Filament Disassembly and Tyrosine Dephosphorylation of FAK, Cas, and Paxillin

Abstract Insulin-like growth factor I (IGF-I) promotes the motility of different cell types. We investigated the role of IGF-I receptor (IGF-IR) signaling in locomotion of MCF-7 breast cancer epithelial cells overexpressing the wild-type IGF-IR (MCF-7/IGF-IR). Stimulation of MCF-7/IGF-IR cells with 50 ng/ml IGF-I induced disruption of the polarized cell monolayer followed by morphological transition toward a mesenchymal phenotype. Immunofluorescence staining of the cells with rhodamine–phalloidin revealed rapid disassembly of actin fibers and development of a cortical actin meshwork. Activation of phosphatidylinositol (PI)3-kinase downstream of the IGF-IR was necessary for this process, as blocking PI 3-kinase activity with the specific inhibitor LY 294002 at 10 μM prevented disruption of the filamentous actin. In parallel, IGF-IR activation induced rapid and transient tyrosine dephosphorylation of focal adhesion proteins p125 focal adhesion kinase (FAK), p130 Crk-associated substrate (Cas), and paxillin. This process required phosphotyrosine phosphatase (PTP) activity, since pretreatment of the cells with 5 μM phenylarsine oxide (PAO), an inhibitor of PTPs, rescued FAK and its associated proteins Cas and paxillin from IGF-I-induced dephosphorylation. In addition, PAO-pretreated cells were refractory to IGF-I-induced morphological transition. Thus, our findings reveal a new function of the IGF-IR, the ability to depolarize epithelial cells. In MCF-7 cells, mechanisms of IGF-IR-mediated cell depolarization involve PI 3-kinase signaling and putative PTP activities.
Relationship between IL‐2 receptor expression and proliferative responses in lymphocytes from HIV‐1 seropositive homosexual men

Previous studies have shown that exogenous IL-2 does not correct the reduction in phytohaemagglutinin (PHA)-induced proliferation of lymphocytes from HIV-1 infected (HIV+) individuals. We investigated the mechanism of this reduction to determine if reduced expression of the complete IL-2 receptor (IL-2R) was responsible. In a series of experiments, PHA-stimulated lymphocytes from a total of 89 HIV- and 93 HIV+ homosexual men from the Baltimore Multicentre AIDS Cohort Study (MACS) were studied to determine the expression of messages for the alpha and beta subunits of the IL-2R, the binding of 125I-IL-2 to high affinity IL-2R, and the effect of IL-2 on cell proliferation. Compared to HIV- donors, PHA-stimulated lymphocytes from most HIV+ donors demonstrated (i) a reduction in high affinity IL-2R expression that correlated with the reduction in the IL-2-induced proliferative response; and (ii) a reduction in expression of both IL-2R alpha- and beta-chain mRNA which may be responsible for decreased high affinity IL-2R expression. However, lymphocytes from some HIV+ individuals had borderline low IL-2-induced proliferation despite normal or elevated expression of high affinity IL-2R. These results suggest that decreased expression of IL-2R may account, at least in part, for the lower proliferative response of cells from HIV+ donors.
Descriptors of irregular particle morphology and powder properties

The description of irregular particle morphology and powder properties may offer unique insights into the performance of materials intended for use in dry powder inhalers. A number of mathematically similar approaches have been used to study these phenomena, all based on evaluating data in terms of irregular oscillations around a mean value. The specific methods described are Fourier, fractal and chaos analysis, stochastic and percolation models. Data describing the morphology of disodium cromoglycate particles, the behaviour of lactose and sodium chloride powders and dispersion of Intal((R)) (disodium cromoglycate/lactose blend) utilizing a Spinhaler((R)) is presented to demonstrate the application of these approaches to dry powder inhaler systems. It is envisaged that these techniques may be used to characterize powders with a view to guiding formulation and that ultimately this may lead to a greater understanding of the nature and magnitude of performance variables.
Minimizing power dissipation in a disk file actuator

The ability to improve a disk file's access-time performance is severely limited by an inverse fourth-power increase in actuator-power dissipation. Two areas are germane to the actuator-power problem: the design of the actuator coil and the design of the control trajectory. Design considerations for optimal solutions in both of these areas are presented. Utilization of power-optimal control in concert with a power-optimized actuator makes possible a head/disk assembly with improved seek-time performance. >
Description of a Digital Cranial Endocast of Bathygenys reevesi (Merycoidodontidae; Oreodontoidea) and Implications for Apomorphy-Based Diagnosis of Isolated, Natural Endocasts

ABSTRACT Relatively few studies of cranial endocasts document intraspecific variation. Here, discrete morphological and morphometric variation from a sample of more than 150 natural cranial endocasts from a single Eocene locality, Reeves Bonebed (hereafter ‘RBB’) from West Texas are documented. The first description of a digital endocast of an oreodont, Bathygenys reevesi, is given to provide comparative data for other oreodont endocasts. The RBB endocasts were originally assigned to B. reevesi, but virtually none has diagnostic craniodental material still attached, and isolated endocasts of other cetartiodactyl species are known from this locality. Consequently, an attempt was made to identify apomorphies on the RBB sample to diagnose specimens to the lowest possible taxonomic level. The RBB endocasts were diagnosed as oreodonts based on the presence of large, rounded casts of the tuberculum olfactorium, but no specimen can be diagnosed to a particular species. The range for most linear measurements for ...
GENDER SEGREGATION AND THE DUAL ECONOMY: A STUDY OF BLUE‐COLLAR OCCUPATIONS IN U.S. MANUFACTURING INDUSTRIES

Gender divisions are embedded in and essential to the structure of capitalist production. While most men and women in the United States both now work for wages, they rarely work together. Gender segregation has been identified as one of the major issues of the earnings gap between men and women. An explanation of the forces responsible for this has been difficult to achieve. Most theories fail to consider the contribution of demand‐side factors to gender segregation. Neo‐Marxist analysis of labour market segmentation and theories of the dual economy have provided new frameworks for investigating these structural or demand‐side features of industrial organisation. The pattern of blue‐collar segregation in US manufacturing industries is examined drawing on these theories. Employment data from the US census is used to identify how the levels of blue‐collar segregation in manufacturing industries are influenced by the industry's location within the core or peripheral sector of the US economy. Many of segregation's proposed remedies stress the role of supply‐side factors. These strategies focus attention almost exclusively on male and female workers and ignore the structure of the workplace. Strategies that ignore the dualistic nature of the US economy offer only partial solutions and may be counter‐productive. If forced to eliminate or reduce segmentation, employers may simply restructure their labour processes in a way that undermines rather than contributes to gender inequality. It is apparent that the pursuit of gender equality in the workplace is intrinsically related to and dependent on the broader efforts of workers to achieve greater control over production, both at the workplace and in the economy as a whole.
Optically detected magnetic resonance study of the phosphorescent states of trans-2,2′-bipyridine, metal-free cis-2,2′-bipyridine and [Zn (bpy)]2+

Abstract The zero-field splitting (ZFS) parameters and sublevel kinetics were determined for the lowest excited triplet states of trans-2,2′-bipyridine (trans-bpy), metal-free cis-bpy and [Zn(bpy)] 2+ in 2-propanol-water mixtures at 1.2 K by a zero-field optically detected magnetic resonance technique. The ZFS E parameter is sensitive to the conformation change of bpy, while the triplet sublevel kinetics are sensitive to both the conformational change and to metal complex formation with Zn 2+ .
The mutagenicity of sodium bisulfite on base‐substitution strains of Salmonella typhimurium

The mutagenic effects of sodium bisulfite on Salmonella typhimurium LT2 strains carrying the hisG46 allele were investigated. Treating the cells with 1 M sodium bisulfite in 0.2 M acetate buffer (pH 5.2) for various time intervals at 37 degrees C resulted in an increase in the yield of mutants above the spontaneous level. The fold enhancement of the mutant yield and the fold enhancement of the mutant frequency were greatest for the parent strain hisG46 with wild type DNA repair; the derived strains with reduced repair capacity responded to a lesser degree. While sodium bisulfite was mutagenic when tested in liquid suspension assays, strain hisG46 did not respond when the standard Ames plate incorporation assay was used. The greater mutagenic response in repair-proficient strains suggests that normal repair capacities may favor the mutagenic activity of sodium bisulfite. Transduction studies demonstrated that mutations of his+ were closely linked to the hisD gene, and probably were in the structural hisG gene itself.
Low Oxygen Enhances Sickle and Normal Erythropoiesis and Fetal Hemoglobin Synthesis in Vitro

Erythropoiesis is increased in cultures of human blood progenitors when oxygen tension is reduced from 20% (room air) to 5% (low oxygen, closer to physiological bone marrow levels). The effects of low oxygen on gamma-globin synthesis and colony growth in methyl cellulose cultures of blood mononuclear cells from normal individuals and patients with sickle cell diseases were examined. Low oxygen increased colony numbers by 1.5- to 2-fold and erythropoietin sensitivity by almost 2-fold. The interval required for maximal colony growth in cultures from patients with sickle cell disease (sickle colonies) was reduced from 17 days in 20% oxygen to 13 days in 5% oxygen. Relative synthesis of gamma-globin was examined by labeling with 3H-leucine and electrophoresis on Triton acid urea polyacrylamide gels. The % gamma was 1.7-fold higher in normal and 1.4-fold higher in sickle cultures on day 13 in low oxygen. On day 16 the expected temporal decline was not seen in low oxygen, and the % gamma was 2-fold higher in normal and 1.8-fold higher in the sickle studies. Hemin increased colony growth and gamma-globin synthesis in normal cultures in air, and the effects of hemin and low oxygen were additive. In sickle cultures, hemin and low oxygen had additive effects on colony growth, but only low oxygen increased gamma-globin synthesis. Interleukin-3 increased colony numbers on day 13, primarily by acceleration of peak growth. Interleukin-3 also increased gamma-globin synthesis in low oxygen in normal but not sickle cultures. Thus, low oxygen increases in vitro sensitivity to erythropoietin, colony numbers, and relative gamma-globin synthesis in normal and sickle cultures.
High error rates for avian molecular sex identification primer sets applied to molted feathers

Molted feathers are becoming increasingly important as a source of DNA for identifying the sex of individuals, and accurate methods for molecular sex identification are needed. Three molecular sex identification primer sets have been developed for use in nearly all nonratite birds, but performance of these primer sets has not been evaluated for molted feathers. For two species of birds, the Ring-necked Pheasant {Phasianus colchicus) and the Scarlet Macaw {Ara macao), we evaluated success and error rates among primer sets using DNA from molted feathers and assessed the percentage of times an incorrect sex would be assigned when analyses are completed in duplicate. Amplification success rates differed among the primer sets for both species, ranging from 67.5% to 89.2% {P = 0.0002 and 0.009), and error rates were high, ranging from 1.9% to 24.2%. Success rates and error rates were not consistent between species and among primer sets. To improve the accuracy of molecular sex identification tests when using molted feathers, we suggest determining acceptable confidence levels in the accuracy of sex assignment, conducting pilot tests to evaluate the performance of different primer sets, and using high-resolution electrophoresis systems to increase detection of errors. SINOPSIS. Tasa alta de error para identificar el sexo usando t?cnicas moleculares con conjutos de sebadores, aplicados a plumas mudadas Las plumas mudadas se est?n convirtiendo un una fuente importante de ADN para identificar el sexo en aves. No obstante, se necesitan m?todos m?s precisos para la identificaci?n molecular del sexo, cuando se utilizan fuentes no invasivas de ADN. Se han desarrollado tres m?todos moleculares para el sexado utilizando sebadores (primers) que son aplicados a aves que no son rat?tidos. Sin embargo, la confiabilidad de los conjutos de sebadores no ha sido evaluada utilizando plumas que hayan sido mudadas. Evaluamos el ?xito y tasa de error, entre conjuntos de sebadores, utilizando el ADN contenido en plumas mudadas de individuos de Phasianus colchicus y Ara macao. Las tasas de ?xito de amplificaci?n entre conjuntos de sebadores, para ambas especies de aves, variaron de 67.5% a 89.2% (P = 0.0002 y 0.009) y las tasas de error fueron altas con un rango de 1.9% a 24.2%. Las tasas de ?xito y las tasas de error no fueron consistente entre las especies y entre conjuntos de sebadores. Sugerimos establecer un m?todo riguroso, para fuentes no invasivas de ADN, a modo de incrementar la precisi?n en la identificaci?n del
Comment on “Cyclopentadienylideneketene: theoretical confirmation of a key infrared band”

Ab initio calculations indicate that the perdeuterium isotope shift of the ketenic stretching mode of cyclopentadienylideneketene is less than 1 cm −1 , which disagrees with the observed shift (9 cm −1 ) of the strong IR band at about 2100 cm −1 in the matrix IR spectrum of o -benzyne. As the calculated isotope shift is more accurate than the calculated frequency itself, until the discrepancy is resolved, the ab initio results of Scott and Radom should not be considered a conclusive confirmation for the assignment of the IR absorption band at 2085 cm −1 , seen in the infrared spectrum of o -benzyne, to the ketenic stretching mode of cyclopentadienylideneketene.
A Prospective Phase 2 Trial of Reirradiation With Stereotactic Body Radiation Therapy Plus Cetuximab in Patients With Previously Irradiated Recurrent Squamous Cell Carcinoma of the Head and Neck

Purpose Salvage options for unresectable locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. Although the addition of reirradiation may improve outcomes compared to chemotherapy alone, significant toxicities limit salvage reirradiation strategies, leading to suboptimal outcomes. We therefore designed a phase 2 protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN. Methods and Materials From July 2007 to March 2013, 50 patients >18 years of age with inoperable locoregionally confined rSCCHN within a previously irradiated field receiving ≥60 Gy, with a Zubrod performance status of 0 to 2, and normal hepatic and renal function were enrolled. Patients received concurrent cetuximab (400 mg/m 2 on day −7 and then 250 mg/m 2 on days 0 and +8) plus SBRT (40-44 Gy in 5 fractions on alternating days over 1-2 weeks). Primary endpoints were 1-year locoregional progression-free survival and National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 graded toxicity. Results Median follow-up for surviving patients was 18 months (range: 10-70). The 1-year local PFS rate was 60% (95% confidence interval [CI]: 44%-75%), locoregional PFS was 37% (95% CI: 23%-53%), distant PFS was 71% (95% CI: 54%-85%), and PFS was 33% (95% CI: 20%-49%). The median overall survival was 10 months (95% CI: 7-16), with a 1-year overall survival of 40% (95% CI: 26%-54%). At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% were alive with progression. Acute and late grade 3 toxicity was observed in 6% of patients respectively. Conclusions SBRT with concurrent cetuximab appears to be a safe salvage treatment for rSCCHN of short overall treatment time.
Performance Advances in Fighter Aircraft: Measuring and Predicting Progress,

Abstract : A new approach has been developed for measuring advances in jet fighter air vehicle performance. The approach recognizes the multiparameter tradeoffs imposed by the development process by simultaneously considering trends in a number of performance areas, rather than treating each area separately. Relationships are established between the time of appearance of an aircraft design and such parameters as specific power, sustained load factor, Breguet range, and payload fraction. Using the approach to project where the current acquisition environment is leading us with respect to fighter performance suggests tnat: (1) U.S. fighter air vehicle performance is presently advancing at a diminishing rate, (2) increasing the rate of advance may be costly, and (3) performance growth opportunities offered by derivative aircraft seem limited. The results raise some questions about the most desirable mix of investment in air vehicle, avionics, and armament technology. (Author)
Ion-assisted codeposition of CaF 2 -rich CaF 2 –TiO 2 composites as infrared-transmitting films

The influence of the TiO2 concentration (≦10 at. %) on the structural and the optical properties of CaF2-rich CaF2–TiO2 composite films fabricated by reactive ion-assisted codeposition are investigated. The composition-dependent properties are found to be similar to those reported for composite films with higher TiO2 concentrations. The surface roughness of CaF2 films and their adhesion to a glass substrate are greatly improved by the addition of a small amount of TiO2. These composite films are quite suitable for IR coatings as a transparent, low-refractive-index material at wavelengths of <10 µm. Two examples, a Fabry–Perot filter and a mid-IR dichroic filter, of applications that use CaF2–TiO2 with 10-at. % TiO2 and Ge as low- and high-refractive-index coating materials, respectively, are presented.
Isoform-Specific Transcriptional Regulation by Thyroid Hormone Receptors: Hormone-Independent Activation Operates through a Steroid Receptor Mode of Coactivator Interaction

Thyroid hormone receptors (T3Rs) are hormone-regulated transcription factors that play important roles in vertebrate homeostasis, differentiation, and development. T3Rs are synthesized as multiple isoforms that display tissue-specific expression patterns and distinct transcriptional properties. Most T3R isoforms associate with co-activator proteins and mediate transcriptional activation only in the presence of thyroid hormone. The pituitary-specific T3Rbeta-2 isoform departs from this general rule and is able to interact with p160 co-activators, and to mediate transcriptional activation in both the absence and presence of hormone. We report here that this hormone-independent activation is mediated by contacts between the unique N terminus of T3Rbeta-2 and an internal interaction domain in the SRC-1 (steroid receptor co-activator-1) and GRIP-1 (glucocorticoid receptor interacting protein 1) co-activators. These hormone-independent contacts between T3Rbeta-2 and the p160 co-activators are distinct in sequence and function from the LXXLL motifs that mediate hormone-dependent transcriptional activation and resemble instead a mode of co-activator recruitment previously observed only for the steroid hormone receptors and only in the presence of steroid hormone. Our results suggest that the transcriptional properties of the different T3R isoforms represent a combinatorial mixture of repression, antirepression, and hormone-independent and hormone-dependent activation functions that operate in conjunction to determine the ultimate transcriptional outcome.
Pharmacokinetics and biodistribution of a monoclonal antibody to Cryptococcus neoformans capsular polysaccharide antigen in a rat model of cryptococcal meningitis : implications for passive immunotherapy

Several investigators have developed monoclonal antibodies against the capsular polysaccharide of Cryptococcus neoformans which have potential therapeutic applications. Using a rat model of C. neoformans meningitis, we studied the biodistribution and pharmacokinetics of a murine anticryptococcal capsular monoclonal antibody (mAb 2H1) after intravenous and intracisternal administration. After intravenous administration of 125I-labelled 2H1 to infected rats, there was no detectable localization of 125I in the brain or cerebrospinal fluid by either gamma-camera imaging of the whole animal or organ scintillation counting. In contrast, direct intracisternal instillation of 2H1 to infected rats resulted in persistent intracranial activity. In addition, the whole body half-life of intravenously administered radio labelled mAb 2H1 was significantly reduced in infected rats compared with uninfected rats. Our observations suggest that if high central nervous system (CNS) levels of mAb are needed to achieve a therapeutic effect in human C. neoformans meningoencephalitis, direct administration of mAb into the cerebrospinal fluid or modification of the mAb to increase penetration into the CNS may be required. Furthermore, higher or more frequent dosing of mAb may be required to maintain therapeutic levels in the presence of infection. This study demonstrates the usefulness of the rat as an experimental system for studying issues related to cryptococcosis.
Forecasting and recombining time-series components by using neural networks

Operations and other business decisions often depend on accurate time-series forecasts. These time series usually consist of trend-cycle, seasonal, and irregular components. Existing methodologies ...
Membrane based electrostatic precipitation

Legislation from the US EPA aimed at governing the release of particles smaller than 2.5 mm into the atmosphere will have a major impact on coal-fired power plants across the USA. Researchers lead by Professor Hajrudin Pasic at Ohio University have come up with a unique design for wet and dry electrostatic precipitators (ESP) that relies on membrane technology to efficiently capture small particles. In this article, some recent results related to particle collection and removal efficiencies, selection of membrane materials and other relevant issues, as well as comparisons with existing ESP technologies are presented.
Transcription factor YY1: structure, function, and therapeutic implications in cancer biology

Transcription factor YY1: structure, function, and therapeutic implications in cancer biology
Automated microscopy as a quantitative method to measure differences in adipogenic differentiation in preparations of human mesenchymal stromal cells.

Abstract Background aims Multipotent stromal cells, also called mesenchymal stromal cells (MSCs), are potentially valuable as a cellular therapy because of their differentiation and immunosuppressive properties. As the result of extensive heterogeneity of MSCs, quantitative approaches to measure differentiation capacity between donors and passages on a per-cell basis are needed. Methods Human bone marrow-derived MSCs were expanded to passages P3, P5 and P7 from eight different donors and were analyzed for colony-forming unit capacity (CFU), cell size, surface marker expression and forward/side-scatter analysis by flow cytometry. Adipogenic differentiation potential was quantified with the use of automated microscopy. Percentage of adipogenesis was determined by quantifying nuclei and Nile red–positive adipocytes after automated image acquisition. Results MSCs varied in expansion capacity and increased in average cell diameter with passage. CFU capacity decreased with passage and varied among cell lines within the same passage. The number of adipogenic precursors varied between cell lines, ranging from 0.5% to 13.6% differentiation at P3. Adipogenic capacity decreased significantly with increasing passage. MSC cell surface marker analysis revealed no changes caused by passaging or donor differences. Conclusions We measured adipogenic differentiation on a per-cell basis with high precision and accuracy with the use of automated fluorescence microscopy. We correlated these findings with other quantitative bioassays to better understand the role of donor variability and passaging on CFU, cell size and adipogenic differentiation capacity in vitro. These quantitative approaches provide valuable tools to measure MSC quality and measure functional biological differences between donors and cell passages that are not revealed by conventional MSC cell surface marker analysis.
Quantifying Color Variation: Improved Formulas for Calculating Hue with Segment Classification

Premise of the study: Differences in color form a major component of biological variation, and quantifying these differences is the first step to understanding their evolutionary and ecological importance. One common method for measuring color variation is segment classification, which uses three variables (chroma, hue, and brightness) to describe the height and shape of reflectance curves. This study provides new formulas for calculating hue (the variable that describes the "type" of color) to give correct values in all regions of color space. Methods and Results: Reflectance spectra were obtained from the literature, and chroma, hue, and brightness were computed for each spectrum using the original formulas as well as the new formulas. Only the new formulas result in correct values in the blue-green portion of color space. Conclusions: Use of the new formulas for calculating hue will result in more accurate color quantification for a broad range of biological applications.
In vivo and in vitro hatching of eggs of Trichosomoides crassicauda

Abstract Eggs of Trichosomoides crassicauda were collected from rat urine on filter paper and placed in capsules covered with Millipore filter paper. When the capsules were fed to rats and either recovered from the feces or removed surgically from the large or small bowel, the eggs were hatched; but if removed while still in the stomach no hatching occurred. Hatching took place within the capsules when they were inserted directly into the small bowel (unless the bile duct was tied off), and when they were in a balloon connected to the small bowel; but no hatching occurred when the capsules were placed free in the peritoneal cavity or in a balloon connected directly to the bile duct. In vitro hatching within the capsules was produced at 37 °C with 0.1 N sodium bicarbonate and 0.03 N sodium dithionite equilibrated with 10% CO 2 to produce a pH of 7.4. Hatching dropped off with pH changes in either direction, but pH adjustment alone without the dithionite did not produce significant hatching.
Human recombination rates are increased around accelerated conserved regions—evidence for continued selection?

Motivation: We hypothesized that recombination rates might be increased at genetic loci that are subject to more intense selection. Here, we test this hypothesis by using a recently published set of accelerated conserved regions and fine-scale recombination rate estimates provided by the HapMap project. Results: We observed that fine-scale recombination rates are increased around conserved noncoding regions that show accelerated evolution in human or chimp, as compared to noncoding regions showing accelerated evolution in mouse and those being conserved between human and fugu. Recombination rates around hominid accelerated conserved regions (ACRs) are furthermore increased as compared to exonic regions. On the other hand, GC-content is reduced around ACRs, excluding a major confounding influence of GC-content on the observed variation in recombination rate. Conclusion: Our observations indicate that selection intensity could be an important determinant of local recombination rate variation and that continued positive selection might act at many ACR loci. Alternatively, a confounding factor needs to be found that causes a congruent signal in recombination rate estimates based on human polymorphism data and in the comparative genomic data. Researchers who consider the explanation involving selection as more likely may expect more common functional sequence variants at ACRs in genetic association studies. Contact: jan.freudenberg@ucsf.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Effect of Diet Composition on Feed Intake and Growth of Chicks Under Heat Stress. II. Constant vs. Cycling Temperatures

Abstract Broiler chicks 5 to 7 weeks of age were subjected to a constant cool (14 ± 1 C) or hot (31 ± 1 C) environment and fed diets varying in fat level and energy and nutrient density. Chicks gained significantly (P≤.01) more body weight in the cool than in the hot environment. In both environments chicks fed high fat or high fat-high density diets gained more weight than those fed diets low in fat, and there was no diet × temperature interaction. When temperatures were cycled diurnally (cool, 14 to 22 C; hot, 22 to 33 C), as would occur under natural conditions, the growth depression due to heat stress was less in chicks fed the diets high in fat. The special benefit of fat at high temperature was probably the result of reduced heat increment. Under constant temperature conditions, chicks in the cool environment, pair-fed at the same level of feed intake as those in the hot environment, gained significantly (P≤.05) more weight than the latter. These data indicated that factors other than reduced feed intake contributed to the growth depression associated with high temperature. Thyroid size was significantly (P≤.05) reduced in chicks held at constant high temperature and slightly but not significantly reduced in chicks subjected to cyclic heat stress. This decrease in thyroid size suggested there is a practical limit on overcoming by nutritional means the deleterious effects of heat stress in broilers.
Experimental studies of the deformation mechanisms of core-shell rubber-modified diglycidyl ether of bisphenol-A epoxy at cryogenic temperatures:

Epoxy polymers, although often used in fiber-reinforced polymeric composites, have an inherent low toughness that further decreases with decreasing temperatures. Second-phase additives have been effective in increasing the toughness of epoxies at room temperature; however, the mechanisms at low temperatures are still not understood. In this study, the deformation mechanisms of a diglycidyl ether of bisphenol-A epoxy modified with MX960 core-shell rubber particles were investigated under quasi-static tensile and impact loads at room temperature and liquid nitrogen temperature. Overall, the core-shell rubber had little effect on the tensile properties at room temperature and liquid nitrogen temperature. The impact strength decreased from neat to 1 wt% and 3 wt% but increased from neat to 5 wt% at room temperature and liquid nitrogen temperature, with a higher impact strength at room temperature at all core-shell rubber loadings. While a large toughening effect was not seen in this study, the mechanisms anal...
Preliminary hazard analysis for safety-critical software systems

The authors identify strategies for conducting preliminary software hazard analysis, which includes software hazard identification, documentation, and review. The goal for such strategies is to improve a system's overall safety by increasing the hazard list's completeness, correctness, and preciseness. Along with presenting these strategies, a framework is introduced for applying them to safety-critical software development. Before explaining the framework and its related strategies, relevant background issues that relate to safety are discussed. >
The Idealization of Technology: Power Relations in an Engineering Department

The management of technological development involves a dilemma; the manager must strive to understand the diverse specializations required to develop new technology, but he must focus on integrating these specializations. The former requires knowledge, the latter power. It is my contention, however, that in technologically-oriented work groups, there is a tendency for the importance of technology to be exaggerated while power issues are ignored. This process is referred to as the idealization of technology. The result is an inattention to organizational goals and cooperative processes. In this essay, the interpretive concept of culture and the psychoanalytic theory of idealization is used to investigate this problem. The framework is applied to an engineering department whose primary work is the development of advanced technological products. The process of idealization distorts organizational reality in such a way that continual distortions are needed, is a cultural mechanism that is used to mediate the ...
Septal structure and function relationships parallel the left ventricular free wall ascending and descending segments of the helical heart.

Objective: Determine if ventricular septum structure and function relationships parallel the left ventricular free wall descending and ascending segments of the helical heart. Methods: Forty pigs (30—38 kg) were studied physiologically by sonomicrometer to determine if septal fiber orientation resembled responses in the free wall. Following pilot studies in the non-bypassed heart, a right ventriculotomy was made to place septum crystals with fiber orientations that were either perpendicular to or reflected simultaneous free wall measurements. Postbypass measurements tested responses to positive (dopamine) and negative (esmolol) inotropic agents. Results: Similar oblique fiber directions were found for baseline percent systolic shortening (SS%) in the free wall and septum; free wall descending and ascending SS% were 21 3% and 10 3%, and 13 2% and 12 2%, respectively, in the septum. Conversely, impaired shortening occurred when transverse fiber direction was tested. Both oblique areas demonstrated comparable time-delay changes between free wall and septal descending and ascending segment at onset (75 11 ms) and termination (86 21 ms) of contraction. Dopamine increased heart rate and caused a similar increase of free wall descending and ascending segment SS% to 24 2% and 14 3% (p < 0.05), and septal SS% response to 16 2% and 15 2% (p < 0.05), and comparable decrease of time-delay changes of shortening between ascending and descending segments of 54 6 ms and 68 10 ms, respectively (p < 0.05). Conversely, esmolol decreased heart rate and similarly reduced SS% in left ventricular free wall (descending: 18 4%; ascending: 7 4%; p < 0.05) and septum (descending: 10 2%; ascending: 10 3%; p < 0.05). Time-delay of contraction between segments was increased to 91 4m s (p < 0.05), but the hiatus at the end of shortening remained unchanged, due to prolonged endocardial contraction. Conclusions: Septal structure and function relationships parallel the left ventricular free wall ascending and descending segments, thereby supporting the helical heart fiber spatial relationships. The oblique fiber orientation may make the septum become the ‘lion of right ventricular function’.
Testicular circulatory isolation in man: comparison of radionuclide angiography with Doppler evaluation.

Testicular circulatory isolation (TCI) holds promise as a method to avoid drug-induced infertility in male patients about to receive cancer chemotherapy. Complete exclusion of blood flow to the testicle is essential to the success of this technique. We have compared the hand-held Doppler probe and radionuclide angiography (technetium-99m pertechnetate) as monitors of testicular blood flow in 10 patients subjected to unilateral TCI. When Doppler evaluation indicated that testicular circulation had been interrupted, the radionuclide angiogram uniformly confirmed and quantified this conclusion. These results validate the hand-held Doppler as an appropriate tool for assessing testicular blood flow in patients undergoing TCI. © 1993 Wiley-Liss, Inc.
The effect of planting design on out-crossing rate and yield in the ‘Hass’ avocado

Abstract Two enzyme loci were used to measure out-crossing rates in pure and inter-planted groves of ‘Hass’ avocados. Both out-crossing rate and yield per tree were found to be significantly higher in the inter-planted grove. Out-crossing rate and yield were significantly correlated overall, but the relationship within groves was too weak for significance. This information should prove useful as a basis for future studies on methods for maximizing avocado fruit production.
Water-soluble multi-cage super tetrahedral uranyl peroxide phosphate clusters

Combination of uranyl, peroxide, phosphate, and counter ions under ambient conditions in aqueous solution over the pH range 5.5–6.5 results in the self-assembly of a large super tetrahedral cluster containing 124 uranyl hexagonal bipyramids and 32 phosphate tetrahedra designated U124P32. With a diameter of 4 nm, U124P32 consists of four symmetrically identical cage clusters, each built from 23 uranyl hexagonal bipyramids and eight phosphate tetrahedra, as well as a central cage defined by 52 uranyl hexagonal bipyramids and 32 phosphate tetrahedra. It is the first uranyl-based cluster that contains multiple cages and it also has the highest number of uranyl ions. U124P32 contains 152 peroxide groups that are bidentate bridges between uranyl ions. Crystals of U124P32 provided structural details, and were dissolved for subsequent small-angle X-ray scattering and electrospray ionization mass spectrometry characterization that indicated U124P32 remains intact upon dissolution in water. Whereas uranyl phosphates are generally insoluble in water, prompting interest in their applications in remediating contaminated water, U124P32 is highly soluble, reflecting the impact of the nanoscale structure on solubility.
Shared losses reduce sensitivity to risk: A laboratory study of moral hazard

Moral hazards are said to occur when one party makes decisions that have potential neg- ative consequences that will either be fully or partially experienced by another party. The present experiment sought to explore moral hazard in a laboratory setting. Participants made choices between certain and risky rewards. On some trials, participants bore the full brunt of a loss if the risky reward was chosen and lost. On other trials, participants believed losses would be shared with another party creating the opportunity for moral hazard. Our design allowed us to measure whether the presence of a moral hazard influenced partici- pants' choice behavior and to quantify the magnitude of this influence. Results suggested that participants were more tolerant of risk when they believed losses would be shared with another party compared to choices when all of the loss would be experienced person- ally. More importantly, concern for the third party losses appeared to exert no influence on choices whatsoever. These results were found when the third party was anonymous (Experiment 1) but also when they met the third party face-to-face (Experiment 2). The relationship between the current results and real-life moral hazards, as well as possible future research directions, is discussed.
A Survey of Factors Contributing to Gay and Lesbian Domestic Violence

Gay and lesbian domestic violence is still a relatively new topic of study; work has been done in this area only since the early 1980s. Thus, little formal research has been published regarding this issue. This article presents a qualitative study of gay male and lesbian perpatrators of domestic violence. By using demographic profiles from 288 clients who had been referred for perpetrator treatment, the author sought to understand whether self-abusive behaviors, involving drugs, alcohol, food and sex are predominant among perpetrators, as well as to explore the prevalence of intergenerational abuse patterns. Analysis revealed a high incidence of personal histories of abuse experiences among gay/lesbian adult perpetrators, as well as a high incidence of secondary abusive behaviors within this sample.
Engaging today's Students in Earth Science 101

It is a sad fact, or perhaps a happy one, that many geoscientists in academia will find themselves in front of a classroom of 100–300 undergraduate nonscience majors, lecturing to them for three hours per week. Whether it is ‘Rocks for Jocks’ or ‘Waves for Babes,’ students often are under the impression that geoscience classes will be the least painful way to fulfill their science credit requirements. The sense of personal anonymity that can accompany large-enrollment classes often results in a different level of student engagement compared with smaller classes. Thus, if students are physically present at all, instructors often have only their much-divided attention. How can professors keep 300 students, even the ones in the back of the classroom who are barely visible, awake and engaged?
Evolutionary implications of developmental instability in parthenogenetic Drosophila mercatorum. II. Comparison of two strains with identical genotypes, but different modes of reproduction

stability is caused by the mode of reproduction per se and is not due to homozygosity, disruption of coadapted gene complexes, or any other feature of the parthenogenetic genome. The increased rate of abortion with parthenogenetic reproduction is caused by a proportional increase in the normal panoply of errors that occur in sexual reproduction but at a much lower rate. Attempts to establish other sexual analogues of laboratory parthenogenetic strains revealed different male sterility factors within several parthenogenetic genomes that could potentially act to prevent hybridization with sexually reproducing ancestors during the incipient stages in the evolution of an entirely parthenogenetic lineage.
Understanding decreased fertility in women carriers of the FMR1 premutation: a possible mechanism for Fragile X-Associated Primary Ovarian Insufficiency (FXPOI)

Fragile X syndrome (FXS) and its associated disorders are caused by the expansion of the CGG repeat in the 5′ untranslated region of the fragile X mental retardation 1 gene (FMR1). The full mutation, defined as >200 cytosine-guanine-guanine (CGG) triplet repeats, causes FXS. Individuals with 55–199 CGG repeats, classified as premutation carriers, are affected by two distinct disorders depending on their premutation status. Disorders associated with premutation carriers include: Fragile X-associated Tremor Ataxia Syndrome (FXTAS) and Fragile X-associated Primary Ovarian Insufficiency (FXPOI). The molecular similarities of FXTAS and FXPOI (e.g. overabundance of FMR1 transcript and intranuclear inclusions) suggest that similar molecular mechanisms underlie both FXTAS and FXPOI. The current hypothesis describes the underlying mechanism for FXTAS as an mRNA gain-of-function mutation, however the underlying mechanism for FXPOI remains unresolved. New data suggests that repeat associated non-AUG (RAN) translation could underlie FXPOI.
Arresting and releasing Staphylococcal α-hemolysin at intermediate stages of pore formation by engineered disulfide bonds

α-Hemolysin (αHL) is secreted by Staphylococcus aureus as a water-soluble monomer that assembles into a heptamer to form a transmembrane pore on a target membrane. The crystal structures of the LukF water-soluble monomer and the membrane-bound α-hemolysin heptamer show that large conformational changes occur during assembly. However, the mechanism of assembly and pore formation is still unclear, primarily because of the difficulty in obtaining structural information on assembly intermediates. Our goal is to use disulfide bonds to selectively arrest and release αHL from intermediate stages of the assembly process and to use these mutants to test mechanistic hypotheses. To accomplish this, we created four double cysteine mutants, D108C/K154C (αHL-A), M113C/K147C (αHL-B), H48C/ N121C (αHL-C), I5C/G130C (αHL-D), in which disulfide bonds may form between the pre-stem domain and the β-sandwich domain to prevent pre-stem rearrangement and membrane insertion. Among the four mutants, αHL-A is remarkably stable, is produced at a level at least 10-fold greater than that of the wild-type protein, is monomeric in aqueous solution, and has hemolytic activity that can be regulated by the presence or absence of reducing agents. Cross-linking analysis showed that αHL-A assembles on a membrane into an oligomer, which is likely to be a heptamer, in the absence of a reducing agent, suggesting that oxidized αHL-A is halted at a heptameric prepore state. Therefore, conformational rearrangements at positions 108 and 154 are critical for the completion of αHL assembly but are not essential for membrane binding or for formation of an oligomeric prepore intermediate.