cssi/SciSciGPT-SciSciNet huggingface dataset:
Dose-dependent effects of pharmaceutical treatments on bone matrix properties in ovariectomized rats.

As both anabolic and anti-catabolic osteoporosis drugs affect bone formation and resorption processes, they may contribute to bone's overall mechanical behavior by altering the quality of the bone matrix. We used an ovariectomized rat model and a novel fracture mechanics approach to investigate whether treatment with an anabolic (parathyroid hormone) or anti-catabolic (alendronate) osteoporosis drugs will alter the organic and mineral matrix components and consequently cortical bone fracture toughness. Ovariectomized (at 5 months age) rats were treated with either parathyroid hormone or alendronate at low and high doses for 6 months (age 6-12 months). Specifically, treatment groups included untreated ovariectomized controls (n = 9), high-dose alendronate (n = 10), low-dose alendronate (n = 9), high-dose parathyroid hormone (n = 10), and low-dose parathyroid hormone (n = 9). After euthanasia, cortical microbeams from the lateral quadrant were extracted, notched, and tested in 3-point bending to measure fracture toughness. Portions of the bone were used to measure changes in the 1) organic matrix through quantification of advanced glycation end-products (AGEs) and non-collagenous proteins, and 2) mineral matrix through assessment of mineral crystallinity. Compared to the ovariectomized group, rats treated with high doses of parathyroid hormone and alendronate had significantly increased cortical bone fracture toughness, which corresponded primarily to increased non-collagenous proteins while there was no change in AGEs. Additionally, low-dose PTH treatment increased matrix crystallinity and decreased AGE levels. In summary, ovariectomized rats treated with pharmaceutical drugs had increased non-collagenous matrix proteins and improved fracture toughness compared to controls. Further investigation is required for different doses and longer treatment periods.
The geography of opportunity: an exploratory spatial data analysis of U.S. counties

Rising inequality and the lingering effects of the most recent economic recession continue to engender negative perceptions of access to opportunity in the United States. While prior research has established the importance of geography in understanding opportunity in metropolitan areas, little attention has been given to the spatial distribution of opportunity outside urban areas or its temporal variation. This article builds on existing frameworks for measuring opportunity to calculate a multidimensional opportunity index for counties in the lower 48 states and the District of Columbia for the years 2000 and 2010. We use exploratory spatial data analysis techniques to map and critically examine the geography of opportunity at both time periods across regions and three distinct county typologies with an emphasis on identifying clusters of high and low opportunity. We find that opportunity decreased on average for all counties from 2000 to 2010 as did its standard deviation, consistent with arguments that opportunity in the U.S. has both declined and converged. While the opportunity index remains highest in metropolitan and urban counties, nonmetropolitan and rural areas fared well with respect to the spatial clustering of high opportunity counties. Clusters of high opportunity counties shifted from the Northeast to Midwest regions, while clusters of low opportunity counties in traditional strongholds of persistent poverty like Appalachia, the Mississippi Delta, and Lower Rio Grande Valley have become more fragmented.
The suboccipitobregmatic circumference

Abstract 1. 1. A device has been described which is useful in outlining fetal head circumferences, and by its employment the suboccipitobregmatic circumference has been outlined in 70 newborn infants. 2. 2. This group represents infants born by different mechanisms, which includes vertex and breech presentation and cesarean section. In addition, 15 infants born following vertex presentation were measured on the fifth to eighth day of infant life. 3. 3. In all instances but one, the suboccipitobregmatic circumference was ovate in shape with the occipital half narrowed and the bregmatic half broadened. 4. 4. During the process of birth the mechanical advantage of anterior internal rotation of the occiput of the flexed fetal head is definitely favored by the shape of the suboccipitobregmatic circumference.
Effects of Fasting During Pregnancy on Maternal and Fetal Weight and Body Composition in Well-Nourished and Undernourished Rats

The effect of a 2-day fast on fetal and maternal weight and composition was determined in ad libitum-fed and food-restricted pregnant and non-pregnant rats. Fasting between days 17 and 19 of gestation resulted in a greater loss of net maternal body weight in ad libitum-fed pregnant than in nonpregnant rats, and also a greater loss of body fat. In contrast, food-restricted pregnant rats, also fasted from day 17 to day 19 of gestation, maintained their net body weight and body fat during the fast as did nonpregnant rats fasted for the same length of time. Fetal weight was not significantly reduced by fasting in the ad libitum-fed rats but was reduced by 25% in the previously food-restricted rats. The results demonstrate that prior maternal nutritional status strongly influences the effects of fasting on the fetus and that maternal nutrient stores are not mobilized for fetal utilization even when fetal growth is markedly impaired.
Killing Them with Kindness: 'Consumer-Friendly' Arbitration Clauses after AT&T Mobility v. Concepcion

In AT&T v. Concepcion, the Supreme Court struck California’s so-called “Discover Bank rule” – a judge-made rule providing that arbitration agreements attended by class action waivers are unenforceable, if those agreements are contained in standard form consumer contracts. But, arguably, Concepcion leaves open and unresolved the viability of a state law challenge to a bilateral arbitration clause which is shown, in a particular case, to impose a forfeiture of the claimant’s ability to vindicate his state law rights. Meanwhile, in the context of federal claims, the Second Circuit in American Express III reaffirmed in light of Concepcion its earlier holdings that a class action waiver contained in an arbitration agreement is unenforceable if it is proven in the individual case that the arbitration clause at issue would force the claimant to shoulder such costs as would prevent the claimant from effectively vindicating its federal statutory rights. On both the state and federal levels, then, cost-based vindication of rights challenges remain a significant concern to corporate defendants looking to exculpate themselves from exposure to aggregate litigation. All of this begs a question this paper seeks to answer: will the robust recognition of cost-based, evidence-backed vindication of rights challenges swallow up the basic ruling of Concepcion, rendering unenforceable arbitration agreements and class action waivers that the Supreme Court has held are otherwise to be enforced?
Mass flux and solid growth in solid 4He: 60 mK - 700 mK

We use the thermomechanical effect to confirm that a flux of atoms takes place in hcp solid ⁴He below ∼600 mK. We find that the flux falls abruptly in the vicinity of 80 mK and rises with further reduction of temperature. Samples freshly made at 60 mK do not allow mass flux and cannot be grown off the melting curve even when raised in temperature to 200 mK. Solids created above ∼300 mK and cooled to 60 mK can be grown further and demonstrate finite mass flux.
Reverse genetics of the largest RNA viruses.

Publisher Summary The capped and polyadenylated genomes of coronaviruses, spanning some 27 to 31 kb, are the largest of all RNA virus genomes, including those of the segmented RNA viruses. This chapter presents the reverse genetics of the largest RNA viruses. Just as all other positive-sense RNA viruses (retroviruses excluded), coronavirus genomic RNA is infectious when transfected into the cells of a permissive host. Therefore, in principle, the most direct way to perform reverse genetics on a coronavirus ought to involve the construction of a full-length genomic complementary DNA (cDNA) clone from which infectious RNA could be transcribed in vitro . The method––targeted recombination––is less direct and more laborious, and so far it has been applied exclusively to site-directed mutagenesis of mouse hepatitis virus (MHV). Thus, at least for structural gene mutations that are not expected to be severely deleterious, targeted recombination may remain the less complicated alternative for the creation of MHV mutants. The chapter discusses targeted RNA recombination, such as development of system, genetic analysis of coronavirus structural proteins, genetic analysis of coronavirus RNA synthesis, and limitations of targeted recombination.
Studies of the immunological capacity of germ-free mouse radiation chimeras. II. Thymus cell function in a humoral immune response to sheep erythrocytes.

Abstract Experiments described here were undertaken to determine the reason for the depressed humoral immune response in germ-free mouse allogeneic radiation chimeras. Indirect immunofluorescence using the theta (θ) antigen as a marker demonstrated that about 10% of the nucleated cells in the spleen of both allogeneic and syngeneic chimeras bear the θ antigen. One type of in vivo cell transfer assay employed to determine the capacity for “helper” function of thymocytes revealed that allogeneic chimera thymocytes were only 7–18% as efficient in “helper” function as normal thymocytes. A second type of in vivo cell transfer assay demonstrated that the presence of intact normal thymic stroma had no effect on the “helper” inefficiency of thymocytes obtained from allogeneic radiation chimeras.
Performance Measurements for Machine-Learning Trading Systems

This study presents several insightful performance measurements for machine-learning trading systems. Machine-learning trading platforms are presumed to operate in a continuous time domain, whereas their learning configurations prompt recurring yet bounded improvements over time. The study provides practical estimation guidelines for the relevant parameters and further illustrates the functionality of the proposed scheme through some conjectural examples. The recommended performance measurements aim to help internal auditors of trading departments and regulatory institutions to better track errors at these automated systems.
Muscarinic receptors transform NIH 3T3 cells through a Ras-dependent signalling pathway inhibited by the Ras-GTPase-activating protein SH3 domain.

Abstract Expression of certain subtypes of human muscarinic receptors in NIH 3T3 cells provides an agonist-dependent model of cellular transformation by formation of foci in response to carbachol. Although focus formation correlates with the ability of the muscarinic receptors to activate phospholipase C, the actual mitogenic signal transduction pathway is unknown. Through cotransfection experiments and measurement of the activation state of native and epitope-tagged Ras proteins, the contributions of Ras and Ras GTPase-activating protein (Ras-GAP) to muscarinic receptor-dependent transformation were defined. Transforming muscarinic receptors were able to activate Ras, and such activation was required for transformation because focus formation was inhibited by coexpression of either Ras with a dominant-negative mutation or constructs of Ras-GAP that include the catalytic domain. Coexpression of the N-terminal region of GAP or of its isolated SH3 (Src homology 3) domain, but not its SH2 domain, was also sufficient to suppress muscarinic receptor-dependent focus formation. Point mutations at conserved residues in the Ras-GAP SH3 domain reversed its action, leading to an increase in carbachol-dependent transformation. The inhibitory effect of expression of the Ras-GAP SH3 domain occurs proximal to Ras activation and is selective for the mitogenic pathway activated by carbachol, as cellular transformation by either v-Ras or trkA/nerve growth factor is unaffected.
Epiphytic Fitness of Phytopathogenic Bacteria: Physiological Adaptations for Growth and Survival

Large numbers of microorganisms flourish on leaves, despite the fact that leaf surfaces are subject to rapid and drastic fluctuations in temperature, radiation and humidity. The bacteria that are found on aerial leaf surfaces are distinct from bacteria in other habitats (JENSEN 1971; STOUT 1960a,b), including the nearby soil, suggesting that they have particular adaptations allowing them to exploit epiphytic environments. Few studies have tested whether bacteria that are not typically found on leaf surfaces can exploit the leaf surface habitat as well as those that are commonly found there. In one such study, O’BRIEN and LINDOW (1989) found that while strains of Salmonella, Escherichia, and Aeromonas species could achieve large population sizes on leaves kept continuously wet under controlled conditions, their populations decreased dramatically upon drying of the leaf surface. In contrast, common epiphytic bacterial species such as Pseudomonas syringae maintained large population sizes on dry leaf surfaces. Although such differences in epiphytic behavior can be demonstrated, the traits that contribute to the unique success of epiphytes in the phyllosphere are poorly understood.
The Peroxisome Proliferator Activated Receptor Gamma (PPARγ) Ligand Rosiglitazone Modulates Bronchoalveolar Lavage Levels of Leptin, Adiponectin, and Inflammatory Cytokines in Lean and Obese Mice

Obese mice that lack leptin receptor (db (-) /db (-)) have been shown to have innate bronchial hyperresponsiveness (BHR). It has been proposed that the obesity-mediated BHR may involve a combination of increased leptin and reduced systemic adiponectin levels. The aim of this study was to determine if obesity modifies the airway concentration of leptin and adiponectin and whether treatment with a synthetic peroxisome proliferator-activated receptor gamma (PPARgamma) ligand can reduce airway leptin and increase airway adiponectin. In this study, obese, leptin receptor-deficient (db (-) /db (-)), or lean (db ( + ) /db (-)) mice were treated with rosiglitazone (3 mg/kg/day) or vehicle by gavage daily for 1 week. Bronchioalveolar lavage (BAL) was subsequently performed to determine levels of leptin, adiponectin, and inflammatory cytokines. Treatment with rosiglitazone increased BAL adiponectin levels in lean (p = 0.04) and to a lesser extent in obese mice (p = 0.07). Rosiglitazone treatment lowered leptin levels in lean mice, but increased leptin levels in BAL fluid of obese mice (p < 0.01). The BAL levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) were lower in the lean rosiglitazone-treated group compared with the obese vehicle-treated group and lower in the obese rosiglitazone-treated group compared with the obese vehicle-treated group. These results demonstrate that obesity is associated with alterations in adipokine and cytokine levels in the airways that can be modulated by treatment with roziglitazone.
Mathematical controllability of genomic networks.

Scientists aim to understand, whereas engineers aim to modify and control. In the study by Rajapakse et al. in PNAS (1) these two objectives come together in the context of genomic reorganization during cell differentiation. Cell differentiation, a branch of epigenetics, is a well-analyzed process but one that lacks a mathematical predictive model. Systems biology provides mathematical tools and has recently become a fertile ground for network science (2, 3), specifically in the understanding of the collective dynamics within the nucleus. Indeed, from genetic networks to organizations, one may postulate that a network paradigm is the correct framework to understand life's complexity (4). The complex interactions within a living cell have benefited both from network science concepts as well as from the availability of computing power (3) to provide some modeling tools. What has been lacking, however, is the coupling of genomic network properties and characteristics, with the ability to affect changes at the cellular level. This ability may be especially powerful if one can steer the behavior of a living organism during cell differentiation. Rajapakse et al. (1) provide a convincing mathematical model that explains distinct phases of genomic reorganization consistent with experimental results and suggest that guiding the reorganization toward biologically desirable states may be possible.
Sex and Gender in the 1980s Heavy Metal Scene: Groupies, Musicians, and Fans Recall Their Experiences

Groupies, heavy metal musicians, and highly devoted fans (metalheads) were some of the most salient identity groups for teenagers and emerging adults in the 1980s—the tail end of the Baby Boom and the beginning of the newly emerging Generation X. Met with appalled reactions from conventional society, the heavy metal scene nevertheless appeared to help at least some disenchanted youth negotiate turbulent times. The present study of 144 middle-aged 1980s groupies, metal fans, and professional musicians used both quantitative and qualitative data to develop insights into the developmental processes of these emerging adults of the 1980s. Metalheads described their childhood experiences, including maltreatment, their sexual and substance use activities in the 1980s, identity issues, and reported on current indicators of adjustment, such as education, mental health, and happiness. The results confirm that youth involved in the metal scene had high rates of substance use, risky sexual behaviors, and especially for groupies, traumatic childhood experiences, as well as drug dependence and sexual violence during their groupie days. However, despite their trauma and risky behaviors, participants were able to thrive and develop healthy adult lives, from which they look back fondly on those 1980s experiences. The richness of these data provide insights into the search for identity for marginalized youth, and provide hypotheses for future research on the understudied developmental processes of such adolescent style cultures.
Role of viruses in the development of atopic disease in pediatric patients.

The prevalence of atopic diseases continues to rise in modernized countries, without a clear explanation for this increase. One potential cause identified from epidemiologic studies of children is respiratory RNA viral infections leading to development of recurrent wheezing, asthma, and allergic sensitization. We review human epidemiologic data that both support and refute the role of viruses in this process. Exploring recent murine models, we document possible immunologic mechanisms that could translate a viral infection into atopic disease. We further discuss evidence for a post-viral “atopic cycle” that could explain the development of multiple allergen sensitization, and we explore available data to suggest a connection between viral infections of the gastrointestinal tract with the development of food allergy. Taken together, this review documents evidence to support the “viral hypothesis”, and, in particular, the role of RNA viruses in the development of atopic disease.
Social capital and team performance

Purpose – This article attempts to contribute to the body of knowledge regarding the value of social networks, or social capital, within the group process towards group and team performance by exploring the explicit contribution of social capital towards a group or team's performance.Design/methodology/approach – The research views the potential contribution of social capital through the perspective of the resource‐based view of organizations, where social capital's unique potential contribution to the organization's competitive advantage is highlighted. Data were collected from undergraduate student‐athletes (n=570) from 23 NCAA colleges and universities across the USA using a multiple hierarchical regression analysis.Findings – Results show a significant connection between social capital and team performance. This contribution is above and beyond other input and process variables, such as past team performance.Research limitations/implications – Data were limited to a cross‐sectional view of social capi...
Ethnic diversity, social sanctions, and public goods in Kenya

Abstract This paper examines ethnic diversity and local public goods in rural western Kenya. The identification strategy relies on the stable historically determined patterns of ethnic land settlement. Ethnic diversity is associated with lower primary school funding and worse school facilities, and there is suggestive evidence that it leads to poor water well maintenance. The theoretical model illustrates how inability to impose social sanctions in diverse communities leads to collective action failures, and we find that school committees in diverse areas do impose fewer sanctions on defaulting parents. We relate these results to the literature on social capital and economic development and discuss implications for decentralization in less developed countries.
Review of the Positive Behavior Support Training Curriculum: Supervisory and Direct Support Editions.

In the past several years, the values and practices of positive behavior support (PBS) have had a significant impact on services provided to adults and children with disabilities. Evidence of this ...
Diffusion, Segregation, and Recrystallization in High-Dose Ion-Implanted Si

Using the new technique of Z-contrast scanning transmission electron microscopy (STEM), we have been able to study the segregation of Sb at an advancing SPE growth interface and the resulting interface breakdown. The first direct information is obtained on Sb diffusion in the amorphous phase, which is many orders of magnitude enhanced over tracer crystalline values. This controls both the dopant incorporation and the stability of the resulting supersaturated alloy. These results are compared to the behavior of the low melting point substitutional diffusers and the interstitial diffusers.
Enthalpy of the B-to-Z Conformational Transition of a DNA Oligonucleotide Determined by Isothermal Titration Calorimetry

The influence of high concentrations of Na(+) or [Co(NH(3))(6)](3+) on the conformation of two related DNA oligomers was investigated by circular dichroism spectropolarimetry (CD), isothermal titration calorimetry (ITC), and differential scanning calorimetry (DSC). As revealed by CD, DNA oligomers, (dC-dG)(4) and (dm(5)C-dG)(4), both form right-handed double helical structures (B-DNA) in standard phosphate buffer with 115 mM Na(+) at 25 degrees C. However, at 2.0 M Na(+) or 200 microM [Co(NH(3))(6)](3+), (dm(5)C-dG)(4) assumes a left-handed double helical structure (Z-DNA), whereas the unmethylated (dC-dG)(4) analog remains right-handed under those conditions. ITC was then used to determine the enthalpy change upon increasing the concentration of either Na(+) or [Co(NH(3))(6)](3+) for both DNA oligomers at 25 degrees C. The titration with Na(+) resulted in endothermic isotherms with (dm(5)C-dG)(4) being more endothermic than (dC-dG)(4) by 700 cal/mol basepair. In contrast, titration with [Co(NH(3))(6)](3+) resulted in exothermic isotherms with (dC-dG)(4) being more exothermic than (dm(5)C-dG)(4) by 720 cal/mol basepair. We attribute the enthalpy difference to the conformational transition from B-form DNA to Z-form DNA for (dm(5)C-dG)(4), a transition which does not occur for the unmethylated (dC-dG)(4). The value of approximately 700 cal/mol basepair for the enthalpy of the B-Z transition compares favorably with previously published results obtained by different techniques. DSC was used to monitor the duplex to single strand transitions for both oligomers under the different concentrations. These results indicated that methylation of the cytidine destabilizes (dm(5)C-dG)(4) relative to (dC-dG)(4). Coupling the DSC data with the ITC data allowed construction of a thermodynamic cycle which gives insight into the influence of both temperature and ionic strength on the heat content of the two DNA systems studied. Further, this study reveals the utility of using ITC for determinations of transition enthalpies with the appropriate choice of control.
Economic impact and technical change

The technology decomposition theory is proposed for technologies that exhibit rapid technical change. This theory is intended to support technology forecasting by means of definition of the technical change in technology constituents. Technology decomposition shows that rapid technical change is mainly accomplished by improvements in the manufacturing process. The improvements are the result of the design of new production equipment. Measurements of technical change are used to derive a technology constituent value. It is proposed that the derived constituent value is the maximum achievable. This leads to implications for the management of technology in general and, specifically, for the management of product engineering, if the product depends on one or more rapidly changing technologies. >
Alignability versus bandwidth and bit-error-rate for optical interconnects

Abstract It is desirable to design an optical interconnect so that it has high bandwidth, signal-to-noise ratio, and alignability. Examining the relationship between the alignability, bandwidth, signal-to-noise ratio, and bit-error-rate shows that increasing the alignability can lead to a simultaneous improvement in the signal-to-noise ratio and bit-error-rate, but a decrease in the bandwidth. It has been shown that, despite these opposing changes, there may exist effective optical interconnect designs that simultaneously satisfy minimum alignability, bit-error-rate, and bandwidth requirements.
Specificity and cross-reactivity of monoclonal and polyclonal antibodies against cytochrome P-450E of the marine fish scup.

Abstract Monoclonal antibody (MAb) 1-12-3 generated against liver cytochrome P-450E (P-450E), an aryl hydrocarbon hydroxylase of the marine fish Stenotomus chrysops (scup), reacted only with P-450E when tested in immunoblot analysis with five P-450 fractions from scup liver. This and six other MAbs against P-450E recognized purified P-450E, as well as a single band in β-naphthoflavone (BNF)-induced scup microsomes that comigrated with authentic P-450E. Like MAb 1-12-3, polyclonal anti-P-450E reacted with P-450Ebut not with other scup P-450 fractions and reacted strongly with a band coincident to P-450E in BNF-treated scup microsomes. However, the polyclonal antibody (PAb) also faintly recognized additional microsomal proteins. MAb 1-12-3 recognized P-450Einduced by 3,3′,4,4′,5,5′-hexachlorobiphenyl and by polychlorinated biphenyl mixtures in scup, and a single band induced by BNF or 3-methylcholanthrene (MC) in microsomes of other teleosts, including two trout species, killifish and winter flounder. The content of the P-450E counterpart in these fish and also in untreated scup coincided with induced ethoxyresorufin O-deethylase (EROD) activity. Induced EROD activity in scup and trout was strongly inhibited by MAb 1-12-3, further demonstrating the relationship between P-450E and inducedP-450in trout. MAb 1-12-3, two other MAbs, and anti-P-450E PAb recognized a band comigrating with P-450c in BNF-induced rat microsomes. MAb 1-12-3 also recognized purified rat P-450c. MAb 1-12-3 and anti-P-450E PAb recognized a second band of lower molecular weight than P-450c in BNF rat microsomes which may correspond to P-450d, the MC- and isosafrole-inducible rat isozyme. The results firmly establish the identity of scup P-450E, the relationship of BNF-induced P-450 in other teleosts with P-450E, and the immunochemical relationship of P-450E with rat P-450c. Furthermore, results with untreated fish suggest that effects of environmental chemicals may be detected by immunoblotting with monoclonal anti-P-450E.
CMOS active pixel image sensor

A new CMOS active pixel image sensor is reported. The sensor uses a 2.0 /spl mu/m double-poly, double-metal foundry CMOS process and is realized as a 128/spl times/128 array of 40 /spl mu/m/spl times/40 /spl mu/m pixels. The sensor features TTL compatible voltages, low noise and large dynamic range, and will be useful in machine vision and smart sensor applications. >
Attitudes and beliefs toward biobehavioural research participation: voices and concerns of urban adolescent females receiving outpatient mental health treatment.

AbstractBackground: Biobehavioural research methodology can be invasive and burdensome for participants – particularly adolescents with mental illnesses. Human biological researchers should consider how methodological impositions may hinder adolescent research participation. However, literature on adolescent’s voices and concerns toward biobehavioural research participation is virtually non-existent.Aim: This study was designed to determine adolescents’ perceptions of participation in research involving the collection of biomarkers via blood, saliva and/or urine samples.Subjects and methods: Urban adolescent females (aged 12–19) receiving outpatient mental health treatment (n = 37) participated in focus groups with concurrent survey administration to explore attitudes, beliefs and willingness/intentions toward biobehavioural research participation.Results: Participants had favourable attitudes toward biobehavioural research and were amenable to provide each specimen type. Mistrust for research emerged, ho...
Structural genomics for Caenorhabditis elegans: high throughput protein expression analysis

Abstract The structural genomics initiatives have begun with the aim to create a so-called ‘basic set library’ of protein folds that will be used to improve protein prediction methods. Such a library is thought to require the determination of up to 10,000 new structures, including representative structures of several sequence variants from each protein fold. To meet this goal in a reasonable time frame and cost, automated systems must be utilized to clone and to identify the soluble recombinant proteins contained in multiple genomes. This paper presents such a system, developed using the genome of Caenorhabditis elegans (19,099 genes) as a model eukaryotic organism for structural genomics. This system successfully automates nearly all aspects of recombinant protein expression analysis including subcloning, bacterial growth, recombinant protein expression, protein purification, and scoring protein solubility.
Caspase-8, -12, and -3 Activation by 7-Ketocholesterol in Retinal Neurosensory Cells

PURPOSE. To determine the caspase pathways involved with 7-ketocholesterol (7kCh)-induced apoptosis in rat R28 cells. METHODS. R28 cells were exposed to 7kCh with or without low-density lipoprotein (LDL) and z-VAD-fmk, a pan-caspase inhibitor. Cell viability was measured by a trypan blue dye exclusion assay. Caspase-3, -8, -9, and -12 activities were measured by fluorochrome caspase assays. ARPE-19 cells were used as control for caspase-3 inhibition experiments. RESULTS. R28 cultures showed decreased cell viability on 7kCh exposure compared with controls (P < 0.001), and this was reversed with LDL and LDL + z-VAD-fmk (P < 0.001). The 7kCh-treated R28 cultures had increased caspase-8 activity compared with controls (P < 0.001). This activity was blocked partially with LDL (P < 0.01) or LDL + z-VAD-fmk (P < 0.001) but not with z-VAD-fmk alone. Caspase-12 activity was increased after 7kCh treatment compared with controls (P < 0.01), and this activity was increased further with the addition of LDL. Caspase-3 activity in R28 cultures increased with 7kCh treatment compared with controls (P < 0.001). In R28 cultures, the z-VAD-fmk treatment did not blocked 7kCh-induced caspase-3 activity but did block activity in ARPE-19 cultures (P < 0.001). Caspase-9 was not activated by 7kCh treatment. CONCLUSIONS. In R28 cells, 7kCh-induced apoptosis involves the caspase-3 along with the caspase-8 and caspase-12 pathways. LDL partially blocked 7kCh-induced caspase-8 activity but increased caspase-12 activities, suggesting that caspase-8 and caspase-12 pathways are independent of each other. The z-VAD-fmk inhibitor blocked caspase-3 activities in the homogeneous ARPE-19 cultures but not in the heterogeneous R28 cultures.
Host-parasite interaction of tyrosine metabolism in rats infected with trypanosoma brucei

Abstract 1. 1. p -Hydroxyphenylpyruvate, the by-product of tyrosine metabolism by T. brusei , was found to be non-toxic to the rat. 2. 2. A model is proposed for host-parasite interaction in the metabolism of tyrosine. 3. 3. Oxygen uptake data suggest a conversion of parasite respiration to the Kreb's cycle during glucose deprivation conditions in the host, fueled by products of tyrosine metabolism.
An HPLC method with UV detection, pH control, and reductive ascorbic acid for cyanuric acid analysis in water.

Every year over 250 million pounds of cyanuric acid (CA) and chlorinated isocyanurates are produced industrially. These compounds are standard ingredients in formulations for household bleaches, industrial cleansers, dishwasher compounds, general sanitizers, and chlorine stabilizers. The method developed for CA using high-performance liquid chromatography (HPLC) with UV detection simplifies and optimizes certain parameters of previous methodologies by effective pH control of the eluent (95% phosphate buffer: 5% methanol, v/v) to the narrow pH range of 7.2-7.4. UV detection was set at the optimum wavelength of 213 nm where the cyanuric ion absorbs strongly. Analysis at the lower pH range of 6.8-7.1 proved inadequate due to CA keto-enol tautomerism, while at pHs of 7.4 proved more sensitive but their use was rejected because of CA elution at the chromatographic void volume and due to chemical interferences. The complex equilibria of chlorinated isocyanurates and associated species were suppressed by using reductive ascorbic acid to restrict the products to CA. UV, HPLC-UV, and electrospray ionization mass spectrometry techniques were combined to monitor the reactive chlorinated isocyanurates and to support the use of ascorbic acid. The resulting method is reproducible and measures CA in the 0.5-125 mg/L linear concentration range with a method detection limit of 0.05 mg/L in water.
Human prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth

Cellular prostatic acid phosphatase (cPAcP), an authentic tyrosine phosphatase, is proposed to function as a negative growth regulator of prostate cancer (PCa) cells in part through its dephosphorylation of ErbB-2. Nevertheless, the direct interaction between cPAcP and ErbB-2 has not been shown nor the specific dephosphorylation site of ErbB-2 by cPAcP. In this report, our data show that the phosphorylation level of ErbB-2 primarily at Tyr1221/2 correlates with the growth rate of both LNCaP and MDA PCa2b human PCa cells. Further, cPAcP reciprocally co-immunoprecipitated with ErbB-2 in a non-permissive growth condition. Expression of wild type cPAcP, but not inactive mutant, by cDNA in cPAcP-null LNCaP C-81 cells results in decreased tyrosine phosphorylation of ErbB-2 including Tyr1221/2. Concurrently, Tyr317 phosphorylation of p52Shc, proliferating cell nuclear antigen expression, and cell growth are decreased in these cells. Conversely, decreased cPAcP expression by short hairpin RNA in LNCaP C-33 cells was associated with elevated phosphorylation of ErbB-2 initially at Tyr1221/2. Its downstream p52Shc, ERK1/2, Akt, Src, STAT-3, and STAT-5 were activated, and cell proliferation, proliferating cell nuclear antigen, and cyclin D1 expression were increased. Stable subclones of C-33 cells by small interfering PAcP had elevated Tyr1221/2 phosphorylation of ErbB-2 and exhibited androgen-independent growth and increased tumorigenicity in xenograft female animals. In summary, our data together indicate that in prostate epithelia, cPAcP interacts with and dephosphorylates ErbB-2 primarily at Tyr1221/2 and hence blocks downstream signaling, leading to reduced cell growth. In PCa cells, decreased cPAcP expression is associated with androgen-independent cell proliferation and tumorigenicity as seen in advanced hormone-refractory prostate carcinomas.
Stability of dietary ascorbic acid and the effect of supplementation on reproductive performance of broiler breeder chickens.

1. The purpose of the study was to determine the stability of dietary ascorbic acid and the reproductive responses of broiler breeder chickens to supplemental 75 mg ascorbic acid/kg diet. 2. Six breeder flocks of 13 000 birds each were studied. Egg production, eggshell porosity, fertility, hatchability and plasma ascorbic acid were measured. 3. Storage of the diets under dry heat resulted in a linear decrease in ascorbic acid content and the rate of decline was 5-fold higher in the supplemented diet. 4. Differences were not detected between treatments in egg production, egg weight, eggshell porosity, fertility, hatchability or plasma ascorbic acid. 5. The results did not provide evidence of a beneficial reproductive response to the inclusion of ascorbic acid in commercial broiler breeder diets.
Specific immunotherapy with vaccinia oncolysates

A live vaccinia virus-augmented tumor cell vaccine (vaccinia oncolysate) has been used as a specific active immune mechanism stimulator against certain advanced human cancers. This preliminary trial, in which the same dose of vaccinia oncolysate was used in 29 patients, showed the vaccine to be safe, non-toxic, and potentially effective. This study was designed as a toxicity/feasibility trial at a single vaccine dose. There was no effort to look at other dose levels. The heterogeneity of this early tumor group only reflects the type of patient available to the study during the early phase of vaccine testing. Randomized prospective trials have begun to make future analysis easier.
Receiver operating characteristic (ROC) analysis of neural code efficacies

Nerve cell signals are different in form from the stimuli that evoke them and they exhibit complex spatio-temporal characteristics. This defines a neural coding problem which is addressed by two current theories: Multiple Meaning Theory holds that neural signals contain patterns that make statements about combinations of stimulus properties; the Task Dependence Hypothesis suggests that different features of identical neural signals mediate performance in different behavioral tasks. These coding issues were addressed by investigating the representation of sensory information in the distal nervous system after transduction of visual stimuli into bio-electric signals. The objects of study were light-evoked neural responses which had been intracellularly recorded from single retinula (photoreceptor) cells in Limulus lateral eyes. The efficacies with which sensory information was represented by various candidate neural codes were calculated using receiver operating characteristic (ROC) analyses to provide objective indices. The specific visual problem under investigation was discrimination between light flashes whose intensities differed by a very small amount. A wide range of light adaptation states and relative stimulus intensities were explored. Extremely stringent data quality standards were applied which restricted the investigation to cells whose potentials did not exhibit any statistically significant drift during the hours required for data collection. Seven cellular characterizations were simultaneously monitored to detect drift in a given cell’s potentials; these characterizations included the value of the membrane potential and the values of six candidate codes. These codes were: the area under the light-evoked receptor potential (RP), the mean value of the RP, the peak height of the RP, the slope of the onset of the RP, the duration required for the RP to drop from its peak by a given amount, and the duration required for the RP to end. The results were: (1) Light adaptation increases efficacy. (2) Thus, light adaptation trades sensitivity for acuity (as characterized by ROC discriminations). (3) Increasing relative light flash intensity also increases efficacy. (4) The efficacies of the various codes are significantly different and fall in the following order: area?peak=mean?duration-end=slope= duration-drop. These findings further demonstrate that arbitrary characterizations of stimulus-response relationships are very likely to be incomplete. They particularly indicate that many commonly used and quite conventional neural analysis strategies may substantially underestimate system performance.
Intergenerational Relationship Quality, Gender and Grandparent Involvement.

This prospective, intergenerational study (N = 181) considered how parent (G1, generation 1)–child (G2, generation 2) relationship quality during adolescence and adulthood is associated with G1’s level of involvement with their 3–4 year-old grandchildren (G3, generation 3). Path model analyses indicated different patterns of results for the involvement of grandmothers and grandfathers with the children of their G2 sons and daughters. Current parent-reported G1-G2 relationship quality was positively associated with G2 report of G1 involvement with G3, especially for G2 daughters. The relations among confounding variables, including geographic distance, socioeconomic status, and grandparent marital status and grandparent involvement with grandchildren were considered. Results highlight the roles of intergenerational relationship quality and gender configuration of the G1-G2 dyad in shaping grandparent involvement with grandchildren.
An implicit Hermite WENO reconstruction-based discontinuous Galerkin method on tetrahedral grids

An Implicit Reconstructed Discontinuous Galerkin method, IRDG (P1P2), is presented for solving the compressible Euler equations on tetrahedral grids. In this method, a quadratic polynomial (P2) solution is first reconstructed using a least-squares method from the underlying linear polynomial (P1) DG solution. By taking advantage of the derivatives in the DG formulation, the stencils used in the reconstruction involve only von Neumann neighborhood (adjacent face-neighboring cells) and thus are compact and consistent with the underlying DG method. The final P2 solution is then obtained using a WENO reconstruction, which is necessary to ensure stability of the RDG (P1P2) method. A matrix-free GMRES (generalized minimum residual) algorithm is presented to solve the approximate system of linear equations arising from Newton linearization. The LU-SGS (lower–upper symmetric Gauss–Seidel) preconditioner is applied with both the simplified and approximate Jacobian matrices. The numerical experiments on a variety of flow problems demonstrate that the developed IRDG (P1P2) method is able to obtain a speedup of at least two orders of magnitude than its explicit counterpart, maintain the linear stability, and achieve the designed third order of accuracy: one order of accuracy higher than the underlying second-order DG (P1) method without significant increase in computing costs and storage requirements. It is also found that a well approximated Jacobian matrix is essential for the IRDG method to achieve fast converging speed and maintain robustness on large-scale problems.
Leveraging on-chip voltage regulators as a countermeasure against side-channel attacks

Side-channel attacks have become a significant threat to the integrated circuit security. Circuit level techniques are proposed in this paper as a countermeasure against side-channel attacks. A distributed on-chip power delivery system consisting of multi-level switched capacitor (SC) voltage converters is proposed where the individual interleaved stages are turned on and turned off either based on the workload information or pseudo-randomly to scramble the power consumption profile. In the case that the changes in the workload demand do not trigger the power delivery system to turn on or off individual stages, the active stages are reshuffled with so called converter-reshuffling to insert random spikes in the power consumption profile. An entropy based metric is developed to evaluate the security-performance of the proposed converter-reshuffling technique as compared to three other existing on-chip power delivery schemes. The increase in the power trace entropy with CoRe scheme is also demonstrated with simulation results to further verify the theoretical analysis.
Cellular requirements for the in vitro induction of specific suppression of antibody responses by immune spleen cells

Feedback regulatory signals to an intermediary suppressor cell may provide the mechanism of the suppression of antibody responses which has been described in cocultures of primed (immune) and unprimed (normal) spleen cells. The active cell(s) in the unprimed spleen population is nonadherent to nylon wool, Sephadex G-10 and glass beads. Lymph node cells and cortisone-resistant thymocytes from normal animals act similarly to normal spleen cells in this coculture system. Spleen cells from homozygous nude mice, unlike their heterozygous thymus-bearing littermates, do not produce a high degree of suppression in coculture with immune spleen cells. These data strongly suggest that the normal cell which interacts with primed cells in the cocultures to produce suppression is of thymic origin. However, spleen cells from neonatally thymectomized mice are suppressive in the presence of spleen cells immune to sheep red blood cells. The unprimed cell(s) active in the suppression are sensitive (in the presence of complement) to antisera directed against the surface markers, Thy-1, Qa-1, Lyt-1, Lyt-2, and Ia. Most of the antiserum treatments abrogated the suppressive capacity of the normal spleen cells only partially. Only treatment with anti-Qa-1 and complement routinely eliminated the ability of these cells to suppress in the cocultures suggesting either low concentration of or inaccessible surface alloantigen on the active cells. Alternatively, more than one Qa-1-positive cell set from the unprimed population may be involved. It is postulated that there is at least one subset of Qa-1-positive T lymphocytes present in unprimed spleen and lymph node cell populations capable of participating in the suppression of specific secondary antibody responses when cocultured with spleen cells from specifically primed animals.
The Dilemma Of Image Quality

We attempt to measure image quality to determine the performance of an optical system so that its range of applicability and the information content of the data collected can be specified. Why is there any problem? Mainly because we always attempt to use as simple a measure as possible to describe what is in fact a fairly complicated process. Furthermore as various measures have been used (and abused!) the technology of system design has always been more sophisticated than the measure was designed for. A simple example of this is the two-point resolution criterion first propounded by Rayleigh. The criterion which only truly applies to the resolution of two incoherent individually unresolved objects is directly applicable to the specification of performance of a telescope in viewing star fields; it is also applicable (under carefully specified and controlled conditions) to a microscope viewing fields of individual cells. However, it is not of much value in specifying performance of a telescope viewing the moon, mars or other planets; or to a microscope viewing a general biological specimen.© (1971) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.