cssi/SciSciGPT-SciSciNet huggingface dataset:
Capacity building in medical education and health outcomes in developing countries: the missing link.

Background: Finding evidence for the link between capacity building in medical education and improved health outcomes in developing countries is an important challenge. We describe the Foundation for Advancement of International Medical Education and Research (FAIMER) Institute, a two year, part-time fellowship in medical education methodology and leadership and its evaluation as a model to bridge this gap by collecting quantitative and qualitative data on intermediary outcomes. Methods: FAIMER has used the following framework of human capacity building programs: 1) identify young and talented individuals with potential to become agents for change; 2) organize and deliver an effective learning intervention that is relevant for the environment; 3) facilitate the opportunity for real-life application of acquired knowledge and skills with support; and 4) promote development of a sustainable career path with opportunities for growth and advancement. Results: Twenty-three percent of curriculum innovation projects were directly related to community health. Of the 35 fellows in the first three classes of the Institute, there have been 11 promotions, 9 peer-reviewed publications and 14 international poster presentations, indicating development of the medical education field. Other qualitative and quantitative program evaluation data are presented. Discussion: The link between capacity building in medical education and improved health can be demonstrated in several ways: align curriculum with local health needs, place learners in community clinical settings, teach basic healthcare workers, become involved in national policy development and develop the field of medical education. Conclusion: While experimental models may not be possible to evaluate the effect of capacity building, methods described may help support the connection between improved medical education and health.
Regulation of neurotransmitter vesicles by the homeodomain protein UNC-4 and its transcriptional corepressor UNC-37/groucho in Caenorhabditis elegans cholinergic motor neurons.

Motor neuron function depends on neurotransmitter release from synaptic vesicles (SVs). Here we show that the UNC-4 homeoprotein and its transcriptional corepressor protein UNC-37 regulate SV protein levels in specific Caenorhabditis elegans motor neurons. UNC-4 is expressed in four classes (DA, VA, VC, and SAB) of cholinergic motor neurons. Antibody staining reveals that five different vesicular proteins (UNC-17, choline acetyltransferase, Synaptotagmin, Synaptobrevin, and RAB-3) are substantially reduced in unc-4 and unc-37 mutants in these cells; nonvesicular neuronal proteins (Syntaxin, UNC-18, and UNC-11) are not affected, however. Ultrastructural analysis of VA motor neurons in the mutant unc-4(e120) confirms that SV number in the presynaptic zone is reduced (∼40%) whereas axonal diameter and synaptic morphology are not visibly altered. Because the UNC-4–UNC-37 complex has been shown to mediate transcriptional repression, we propose that these effects are performed via an intermediate gene. Our results are consistent with a model in which this unc-4 target gene (“ gene-x ”) functions at a post-transcriptional level as a negative regulator of SV biogenesis or stability. Experiments with a temperature-sensitive unc-4 mutant show that the adult level of SV proteins strictly depends on unc-4 function during a critical period of motor neuron differentiation. unc-4 activity during this sensitive larval stage is also required for the creation of proper synaptic inputs to VA motor neurons. The temporal correlation of these events may mean that a common unc-4 -dependent mechanism controls both the specificity of synaptic inputs as well as the strength of synaptic outputs for these motor neurons.
Development of a shock-induced detonation driver

A shock tube’s performance can be improved by using a detonation driver that produces a driver gas with a high pressure, a high temperature, a low specific heat ratio and a high speed of sound. Major drawbacks, however, are that the gaseous detonation products have high molecular weight compared to helium and the potential danger. The detonation driver technique, while not new, has been re-examined lately [1,2].
A Response: The Concept of the Classroom Ecology and the Roles of Teachers in Materials Use

The article discusses the use of teaching materials in the teaching of languages. Topics discussed include the concept of classroom ecology and the role of teaching materials in the classroom, the role of language teachers in the use of materials, and suggested next steps for research into language acquisition.
Knowledge of Trainees in School Psychology about Children's Legal Rights:

false." Response frequencies for each of the 39 items by groups were computed. In only two instances were statistically significant item differences noted between groups. Interns more accurately recognized their statutory responsibility to report children suspected of being abused (t = 2.36, p < .03) and that students have a limited right to due process when facing suspension (t = 2.95, p < .02). For the remaining 37 items no significant differences existed between the two groups. Of the interns and incoming students, responses to 41% and 56% of the items, respectively, indicated that legal knowledge was either uncertain or incorrect. There were no clear differences between the two groups in knowledge of children's legal rights. Patterns of responses suggest that over-all the students in a program for school psychology of one midwestern state university have a fairly good understanding of legal issues pertaining to juvenile court procedures, school vandalism, and school attendance requirements. For the remaining eight legal themes, at best respondents have only a limited, and sometimes incorrect, legal knowledge. To be responsive to the contemporary litigious society, school psychologists require an adequate legal preparation. This implies that the trainees' legal knowledge should be accurate, current, and reflect precedents. Such important and complex information needs to be taught formally rather than fortuitously absorbed.
Lung Deposition Analyses of Inhaled Toxic Aerosols in Conventional and Less Harmful Cigarette Smoke: A Review

Inhaled toxic aerosols of conventional cigarette smoke may impact not only the health of smokers, but also those exposed to second-stream smoke, especially children. Thus, less harmful cigarettes (LHCs), also called potential reduced exposure products (PREPs), or modified risk tobacco products (MRTP) have been designed by tobacco manufacturers to focus on the reduction of the concentration of carcinogenic components and toxicants in tobacco. However, some studies have pointed out that the new cigarette products may be actually more harmful than the conventional ones due to variations in puffing or post-puffing behavior, different physical and chemical characteristics of inhaled toxic aerosols, and longer exposure conditions. In order to understand the toxicological impact of tobacco smoke, it is essential for scientists, engineers and manufacturers to develop experiments, clinical investigations, and predictive numerical models for tracking the intake and deposition of toxicants of both LHCs and conventional cigarettes. Furthermore, to link inhaled toxicants to lung and other diseases, it is necessary to determine the physical mechanisms and parameters that have significant impacts on droplet/vapor transport and deposition. Complex mechanisms include droplet coagulation, hygroscopic growth, condensation and evaporation, vapor formation and changes in composition. Of interest are also different puffing behavior, smoke inlet conditions, subject geometries, and mass transfer of deposited material into systemic regions. This review article is intended to serve as an overview of contributions mainly published between 2009 and 2013, focusing on the potential health risks of toxicants in cigarette smoke, progress made in different approaches of impact analyses for inhaled toxic aerosols, as well as challenges and future directions.
Abstract B83: Loss of the Hippo pathway effector Yap disrupts pancreatic morphogenesis and exacerbates exocrine pancreatitis.

Background: The Hippo signaling pathway regulates organ size by restricting the activity of the transcriptional co-activator yes-associated protein (YAP), an oncogene implicated in pancreatic cancer. However, the role of YAP in mammalian pancreatic development and homeostasis is not well understood. Methods: Yap was conditionally ablated in the murine pancreas, either during development, using Pdx1-Cre as a “driver” or in the post-natal exocrine pancreas, using tamoxifen-inducible elastase (Ela)-Cre-ERT2 mice. Exocrine pancreatitis was induced by intraperitoneal caerulein administration. Results: Pdx1-Cre;Yapflox/flox mice demonstrated perinatal lethality (29/33 mice), secondary to a malformed pancreas, underscoring the importance of an intact Yap effector for pancreatic development. In wild-type mice, caerulein pancreatitis was associated with nuclear translocation of Yap protein, and upregulation of its bona fide transcriptional targets, survivin, and connective tissue growth factor (CTGF). Caerulein administration in tamoxifen-induced Ela-Cre-ERT2;Yapflox/flox mice resulted in markedly severe (necrotizing) pancreatitis, including the onset of mortality, compared to littermates with retained pancreatic Yap expression. Transcriptional profiling confirmed the failure to induce multiple anti-apoptotic molecules, including survivin, in the absence of Yap protein, which was accompanied by an increase in acinar cell apoptosis. However, neither exocrine regeneration itself, nor the upregulation of canonical signaling pathways implicated in regeneration (Notch and Hedgehog), was significantly abrogated in the absence of Yap. Conclusions: An intact Hippo pathway is essential for pancreatic morphogenesis. In the mature pancreas, absence of Yap profoundly exacerbates exocrine pancreatitis, with subsequent tissue regeneration remaining largely unaffected. Systemic therapeutics directed at negating YAP function in cancer cells need to be cognizant of the requirement for sustained YAP signaling in embryonic and mature tissues. Citation Format: Sonal Gupta, Anirban Maitra, Ji-Kon Ryu, Nailing Zhang, Seungmin Bang, Meritxell Rovira, Hanno Matthaei, Seung-Mo Hong, Steven D. Leach, Duojia Pan. Loss of the Hippo pathway effector Yap disrupts pancreatic morphogenesis and exacerbates exocrine pancreatitis. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B83.
Superoxide generation by lipoxygenase in the presence of NADH and NADPH

Abstract The ability of soybean lipoxygenase to mediate NAD(P)H oxidation and concomitant Superoxide generation in the presence of linoleic acid was examined. At optimum pH of 8.3, lipoxygenase oxidized both NADH and NADPH in the presence of 700 μM linoleic acid. The oxidation of NAD(P)H was biphasic. The initial rates of NADH and NADPH oxidation were 130 and 140 nmoles/min/nmole of enzyme respectively and the corresponding final rates were 344 and 350 nmoles/min/nmole of enzyme. The apparent Km values calculated for NADH and NADPH oxidation were 13 ju.m and 117 μM respectively. NAD(P)H oxidation was accompanied by the reduction of either ferricytochrome c or nitroblue tetrazolium (NBT) which can be abolished (approx. 85%) by Superoxide dismutase (SOD) suggesting the generation of Superoxide anion radicals. Under optimal conditions, the rates of Superoxide generation, measured as the SOD-inhibitable reduction of ferricytochrome c, were 325 and 235 nmoles/min/nmole of enzyme for NADH and NADPH respectively. Under identical experimental conditions, the SOD-inhibitable NBT reduction rates were 308 and 210 nmoles/min/nmole of enzyme for NADH and NADPH respectively. Both NADH and NADPH could be regenerated after oxidation using the appropriate dehydrogenases. These results strongly suggest that lipoxygenase not only generates lipid hydroperoxides but can also generate Superoxide via oxidation of pyridine nucleotides and may, therefore, significantly contribute to oxidative stress in cells.
Isolation of cardiac myofibrils and myosin light chains with in vivo levels of light chain phosphorylation.

Abstract Conditions are described for the preparation of functional myofibrils and myosin light chains from freeze-clamped beating hearts with the state of light chain phosphorylation chemically ‘frozen’ during the extraction procedure. Myofibrils were shown to be functionally intact by measurement of Ca 2+ binding and ATPase activity. Highly purified cardiac myosin light chains could be routinely isolated from myofibrillar preparations using ethanol fractionation together with ion-exchange chromotography. Analysis of light chains for covalent phosphate indicated that basal levels of phosphorylation of the 18−20 000 dalton light chain of myosin in rabbit hearts beating in situ or in a perfusion apparatus were 0.3–0.4 mol/mol. Covalent phosphate content of the light chain fraction did not change during perfusion of hearts with 10 μM epinephrine.
Quantifying the potential benefit of CA 125 screening for ovarian cancer

We develop a stochastic model of screening for ovarian cancer with serum levels of the CA 125 radioimmunoassay, a tumor-specific marker. The natural history of the disease is constructed using a four stage model characterized by a multivariate distribution for duration in each stage. Preserving its important features, we simplify the model to a function of two parameters; the average duration in stage I and the coefficient of variation of duration in each stage. A yearly screening program is superimposed using exponential CA 125 growth curves which result in stage-specific sensitivities corresponding to values reported in the literature. By implementing a computer simulation of the stochastic model, we estimate the benefit due to screening. This benefit is expressed as expected years of life saved per case of ovarian cancer. The model incorporates the stochastic nature of the disease process, allows easy analysis of repeated screens, and automatically accounts for correlation between subsequent tests. It provides the basis for planning optimal screening strategies with CA 125 testing.
Characterizing post-fire vegetation recovery of California chaparral using TM/ETM+ time-series data

A time series of normalized difference vegetation index (NDVI) data derived from 11 TM/ETM+ images was used to examine the recovery characteristics of chaparral vegetation in a small watershed near Santa Barbara, California following a fire event in 1985. The NDVI recovery trajectory was compared to a generalized recovery trajectory of leaf area index (LAI) for the same region, which was established using a chronosequence approach and TM/ETM+ data. Post-fire NDVI recovery trajectories were derived for the entire catchment and for individual vegetation types. Post-fire NDVI spatial patterns on each image date were compared to the pre-fire pattern to determine the extent to which the pre-fire pattern was re-established, and the rate of this recovery. Results indicated that the post-fire recovery trajectory for the catchment area average NDVI was similar to the previously established regional LAI trajectory based on a chronosequence approach. The NDVI recovery was disrupted by drought stress and attained pre-fire levels approximately 10 years after the fire. Individual vegetation types did not exhibit different rates of recovery and the recovery trajectories were only distinguished by the maximum post-fire NDVI observed after 10 years. The post-fire NDVI spatial pattern also showed a systematic return to pre-fire conditions, but exhibited a more substantial disruption due to drought stress than was the case for the average NDVI recovery trajectory.
The Ecology of Family Guidance in Low-Income Mexican-American and European-American Families*

This two-part study applied an ecocultural perspective to socialization of daily and long-term goals in low-income Mexican-American and European-American families with children in third, fifth, and seventh grades. The first part of the study examined family members' participation and parents' socialization goals and guidance strategies for their children's daily household chores and homework activities. The second part of the study examined parents' long-term aspirations and guidance strategies for their children's educational, vocational, and moral development. For daily activities, results showed that in Mexican-American families both parents and siblings played important roles, whereas in European-American families parents were the primary socialization agents. As predicted, in both groups parents' expertise influenced their guidance strategies. Finally, Mexican-American and European-American parents differed in their relative endorsement of gender, relational, and self-reliance goals for household chores. For long-term goals, parents in both groups held high educational, vocational, and moral aspirations for their children. However, some parents of seventh-graders had lower educational and vocational aspirations than those of fifth- and third-graders. Although expertise consistently influenced Mexican-American parents' guidance strategies, the pattern for European-American parents was mixed. The discussion highlights between- and within-group differences in daily and long-term socialization practices with an emphasis on resources and vulnerabilities in the families.
Effects of graded perfusion and isovolumic work on epicardial and venous adenosine and cytosolic metabolism.

Abstract Epicardial adenosine levels and venous adenosine release were measured in isovolumically contracting (ISO) and empty non-isovolumic (non-ISO) guinea-pig hearts subjected to graded perfusion (∼ 7.5, 5.5, 4.0, 2.0, and 1.0 ml/min/g). Myocardial metabolism was monitored using 31 P-NMR spectroscopy. At flows of 5.5 ml/min/g or higher epicardial adenosine levels were stable and comparable in ISO and non-ISO hearts (∼ 160 n m ). At flows of 4.0 ml/min/g or higher venous adenosine release was stable and comparable in ISO and non-ISO hearts (∼ 30 pmol/min/g). At lower flows, epicardial adenosine and venous adenosine release both increased and were significantly higher in ISO hearts, compared to non-ISO hearts, at each flow rate. Whereas epicardial adenosine increased linearly in ISO and non-ISO hearts at low flows, venous adenosine release stabilized in ISO hearts perfused at 1.0 ml/min/g. Epicardial adenosine, venous adenosine release, and log [ATP] [ADP] [P i ] all displayed significant correlations with the O 2 supply: demand ratio which were comparable in ISO and non-ISO hearts. Elevated levels of epicardial adenosine were linearly related to log [ATP] [ADP] [P i ] and cytosolic [AMP] and these relationships were comparable in ISO and non-ISO hearts. Alternatively, changes in venous adenosine release did not display simple relationships with log [ATP] [ADP] [P i ] and cytosolic [AMP] and they were not comparable in ISO and non-ISO hearts. The data indicate that: (i) myocardial adenosine formation increases only below a metabolic threshold corresponding to log [ATP] [ADP] [P i ] = 5.0 and O 2 supply:demand = 1.5 in ISO and non-ISO guinea-pig hearts; (ii) stimulated epicardial adenosine levels appear to be consistently related to changes in cytosolic metabolism below this threshold in ISO and non-ISO hearts; (iii) more complex relationships exist between venous adenosine release and myocardial metabolism during graded perfusion, possibly reflecting the variety of factors modulating venous adenosine release.
HIV infection, aging, and immune function: implications for cancer risk and prevention

Purpose of review Combination antiretroviral therapy (ART) has turned HIV infection into a complex chronic disease. This article documents cancer risk among HIV-infected persons, reviews immune system effects of HIV infection in relation to cancer risk, discusses implications for cancer prevention, and suggests future research directions.
Primary afferent stimulation acts through a 193 base pair promoter region to upregulate preproenkephalin expression in dorsal horn of transgenic mice.

Abstract The expression of the principal opioid peptide gene, preproenkephalin A, is exquisitely regulated by primary afferent inputs to the spinal and medullary dorsal horns. This regulated expression in response to neural synaptic activity has been referred to as trans-synaptic regulation. To define which DNA regions could mediate this trans-synaptic regulation, transgenic ‘HEC’ mice whose genomes include 193 bp of the human preproenkephalin A promoter fused to a chloramphenicol acetyltransferase (CAT) reporter gene were studied. Mice received unilateral electrical stimulation of the trigeminal ganglion or adjuvant injection into the hindpaw, stimuli known to regulate dorsal horn proenkephalin expression in vivo. CAT activity conferred by this promoter displayed trans-synaptic upregulation with both stimuli. Although the level of the upregulation was 2- to 3-fold higher than the change in the wild type gene, several features of this induction paralleled aspects of the behavior of the wild-type gene: the rapidity of responses to trigeminal ganglion stimulation, the stimulation intensity dependence of responses to trigeminal ganglion stimulation and the time course of upregulation noted following adjuvant injection. Regulatory proteins binding to this restricted promoter region are thus likely to mediate aspects of dorsal horn enkephalin regulation by pain and other somatic stimuli.
Rheology of Colloidal Suspensions and its Implication for Tank Waste Processing

The rheology of colloidal suspensions can vary enormously depending on the contents of the suspensions and the details of how they were produced. Certain interactions between particles within colloidal suspensions can greatly affect their rheology which can be a serious impediment to their processing. For example, at DOE’s Hanford site, the radioactive tank wastes are very concentrated and have formed a sludge that is too viscous to process. We are interested in understanding the rheology of this system in order to develop an efficient method for processing the waste. Towards this end we have developed a model silica system for the tank wastes whose particles can interact through chemical bonding, Keesom interactions, and Coulombic interactions. Through systematic variation of the solvent and the particle concentration we can alter the rheological behavior from shear thickening to shear thinning to Newtonian. We present preliminary results for this system as it applies to the processing of the tank waste at Hanford.
Applying general strain theory to examine perceived discrimination's indirect relation to Mexican-heritage youth's alcohol, cigarette, and marijuana use.

Latent growth curve modeling was used to test four hypotheses. First, this study hypothesized that acculturation-related variables (e.g., Mexican-heritage youth’s country of origin, time spent in the U.S., and language preference with family and friends) would be associated with initial levels of perceived discrimination. Guided by general strain theory (GST), this study then posed a second hypothesis: Initial levels of perceived discrimination would be indirectly related to initial levels of substance use through initial levels of acculturation stress. Third, this study hypothesized that changes in perceived discrimination would be indirectly related to changes in substance use through changes in acculturation stress. As a fourth hypothesis, it was postulated that initial levels of perceived discrimination would be indirectly related to changes in substance use through changes in acculturation stress. Mexican-heritage youth (N = 1,106) from 29 schools in Phoenix, AZ completed surveys at six waves from 5th through 8th grades. In partial support of the first hypothesis, more time spent in the U.S. and speaking English with friends were associated with lower levels of perceived discrimination. The second hypothesis was not supported. Initial levels of perceived discrimination were positively associated with initial levels of acculturation stress; however, this association was not found between initial levels of acculturation stress and substance use. The third and fourth hypotheses were supported, which buttressed predictions derived from GST. Both initial levels and increases in perceived discrimination were indirectly related to increases in substance use through increases in acculturation stress.
Utilizing Bath/Wafer Contamination Correlation to Validate a Pre-Gate Cleaning Strategy

The correlation of contaminants in a process bath with contaminants on a silicon wafer prepared in the bath is important information when developing a cleaning strategy. In this paper, we present such a correlation focused on contaminants in dilute HF (1:100) and in SC1 (1:1:5 and 1:1:80 at 50°C and 65°C). We have limited the contamination levels to between 0 and 150 ppb. We have also limited the contaminants studied to those that are most likely to be a problem (Fe, Al, Mg, Ca, Cu, Zn, and Na). The bath concentrations are measured using ICPMS and the wafer surface concentrations are measured using both VPD/TXRF and VPD/ICPMS. We demonstrate that Fe and Ca at the levels studied do not deposit from dilute HF, while Cu deposits, showing a linear dependence on bath concentration. We also demonstrate that in the SCl bath, both concentration and temperature are important variables in the contamination of wafers for a given bath contamination level. Al and Zn contaminate wafers most strongly, with Al being the largest contributor at the higher concentration of SC1 and Zn being the largest contributor in the lower concentration. Finally, we demonstrate that a dilute HF clean can remove everything deposited in a highly contaminated SC1 bath.
Sleep and the Housing and Neighborhood Environment of Urban Latino Adults Living in Low-Income Housing: The AHOME Study

Sleep is implicated in the risk of many chronic diseases; however, little is known about the living conditions that influence sleep. In this study of 371 low-income Latino residents, household crowding was associated with reduced odds of long sleep duration relative to average and short sleep duration. Neighborhood disorder and perceived building problems were associated with more sleep disturbances and poor sleep quality. Building problems were associated with prolonged sleep latency. There was a significant cumulative effect of adverse housing and neighborhood conditions on sleep outcomes. These results show that adverse conditions of both the housing and neighborhood environments are associated with poor sleep outcomes.
Nutrient uptake by rice in response to water management

Abstract All rice (Oryza sativa L.) production in the United States utilizes flood irrigation. Yet, depletion of the aquifer in eastern Arkansas may necessitate the adoption of rice production practices that reduce water inputs. Field studies were conducted to evaluate reductions in the duration of floodwater application on nutrient uptake by lowland irrigated rice. Three water management treatments, (i) recommended application of a flood applied at the 4‐ to 5‐leaf stage of development (normal flood), (ii) a delay in the application of the flood until panicle differentiation (delayed flood), and (iii) full‐season intermittent flush irrigation (flush irrigated), were imposed on the cultivar Tebonnet’ grown on a Crowley silt loam (Typic Albaqualfs). Nitrogen (N) was applied as a recommended three‐way split to all treatments. Uptake and tissue concentration of N, phosphorus (P), potassium (K), zinc (Zn), iron (Fe), and manganese (Mn) were determined. Rice subjected to normal flooding consistently responded ...
Some Characterizations of Stockpiling Behavior Under Uncertainty

The objective of this note is to gain new theoretical insights into stockpiling phenomena. The model used to derive our results envisions consumers as responding optimally to uncertainties in the promotion environment. We show that, all else being equal, consumers will stockpile a promoted product more intensely: (i) the lower the availability of deal opportunities, (ii) the smaller the expected deal discount, and (iii) the lower the uncertainty about the deal/regular price, provided that dealing occurs with high/low frequency.
Inhibin‐B Levels in Healthy Young Adult Men and Prepubertal Boys: Is Obesity the Cause for the Contemporary Decline in Sperm Count Because of Fewer Sertoli Cells?

Inhibin-B is a heterodimeric glycoprotein produced by Sertoli cells. Although inhibin-B levels are low when seminiferous tubules are damaged, studies in normal monkeys reveal that inhibin-B levels also correlate positively with Sertoli cell number. In this study, we measured inhibin-B levels in healthy young adult men aged 18-24 years and in prepubertal boys aged 5-9 years in relation to body mass index (BMI). Inhibin-B levels declined with increasing obesity in young adult men; values were 26% lower in men who were obese compared to normal-weight men. Sex hormone-binding globulin and total testosterone, but not free testosterone, were also lower with increasing BMI; serum follicle-stimulating hormone and luteinizing hormone levels were unaffected by obesity. In prepubertal boys, by contrast, inhibin-B was unaffected by obesity. We propose that reduced levels of inhibin-B indicate that obese men have fewer Sertoli cells than men of normal weight. Moreover, normal values in obese prepubertal boys suggest that the effect of obesity on inhibin-B is established during puberty. Finally, because each Sertoli cell is thought to support a finite number of germ cells, fewer Sertoli cells in obesity may predispose to a lower sperm count in adulthood. We speculate that the escalating prevalence of obesity and insulin resistance among adolescents might negatively influence male reproductive function for the next generation.
Calcium-Calmodulin Competes with Actin for Binding to the M-Domain of Cardiac Myosin Binding Protein-C

The regulatory M-domain of cardiac myosin binding protein-C (cMyBP-C) binds to myosin, actin, and to calmodulin when calcium is present (i.e., calcium-calmodulin), but it is unclear whether binding of all three ligands is independent or if binding interactions are competitive. Here we investigated whether calcium-calmodulin (Ca-Cam) binding to the M-domain affected the ability of the M-domain to bind to actin using cosedimentation binding and calmodulin-sepaharose pull-down assays. Results of actin cosedimentation binding assays showed that Ca-Cam significantly reduced specific binding of a recombinant protein containing three N-terminal domains of cMyBP-C (i.e., C1-M-C2, referred to as C1C2) when 10 μM calmodulin was present in the presence of calcium (pCa 3.0). In the absence of calcium (at pCa 10.0) calmodulin had no effect on C1C2 binding to actin. Increasing Ca-Cam concentrations to achieve higher molar ratios with respect to C1C2 further reduced the amount of C1C2 that bound to actin. Conversely, in calmodulin-sepharose pull-down experiments, binding of C1C2 to calmodulin was only modestly reduced in the presence of increasing concentrations of F-actin. Taken together, these results indicate that binding of Ca-Cam can compete with actin for binding to the M-domain. These results suggest a potential mechanism whereby the functional effects of cMyBP-C binding to actin can be regulated by calcium. This work supported by NIH HL080367.
Association of age-dependent liver injury and fibrosis with immune cell populations.

Background & Aims The liver's response to injury is fibrosis, and when chronic, cirrhosis. Age is a critical factor impacting many immune-mediated processes, potentially including the liver's wounding response to injury. Methods The effects of age on acute and chronic liver injury were evaluated using a carbon tetrachloride model in mice. Lymphocyte and macrophage populations were assessed by flow cytometry and immunohistochemical analysis. Results Acute liver injury was greater in 18-month-old (old) mice than in 9-month-old (middle-aged) mice as judged by changes in aminotransferases. Similarly, livers of 18-month-old mice had a significantly greater fibrogenic response to injury than did livers of 9-month-old mice after chronic injury (assessed by col1α1 mRNA expression, morphometric analysis and hydroxyproline measurement). Interestingly, livers from young mice (6 weeks old) also exhibited an increase in fibrogenesis compared to 9-month-old mice, albeit not to the same degree as in old mice. Consistent with a role for macrophages in fibrogenesis, the number of liver macrophages in young and 9-month-old mice increased, while in chronically injured livers of 18-month-old mice, the number of macrophages was reduced, and was less than in the livers of young and 9-month-old injured livers. Conclusions Our data indicate that the fibrogenic response to injury varies substantially with age, and moreover that macrophage recruitment and dynamics may be an important component in differential age-associated fibrotic disease.
Hungary's two‐vote’ electoral system

’Arguably the most complex parliamentary voting system in the world’. The following article describes the formulation of Hungary's ‘two‐vote’ system.
CO2 capture using particulate silica aerogel immobilized with tetraethylenepentamine

Abstract A high capacity CO2 sorbent was developed using high porosity hydrophilic and hydrophobic silica aerogel impregnated with tetraethylenepentamine (TEPA). Aerogel sorbents were characterized by thermogravimetric analysis, Fourier transform infrared spectroscopy, and nitrogen adsorption porosimetry for confirming the TEPA loadings and examining the residual porosity after modification. The aerogel sorbents appear to shrink during the drying step of amine impregnation while the surface chemistry of the support is altering the TEPA distribution within the pores. The adsorption performance was tested under pure and low CO2 partial pressure conditions at 75 °C where the hydrophilic aerogel sorbents outperformed the hydrophobic sorbents. The 80 wt.% TEPA loaded hydrophilic sorbent achieved the largest capacity of 6.1 mmol/g in pure CO2 while also attaining 3.5 mmol/g under a dry 10% CO2/Ar stream. The sorbent also showed excellent cyclic stability having a working CO2 sorption capacity of 5.1 mmol/g over 10 cycles.
Reconstructing and Deconstructing the Quest of the Historical Jesus

Those scholars who have assiduously ignored the quest for the historical Jesus because it was unintelligible, incoherent or just uninteresting must now take notice. With the publication of Jesus and Judaism [SCM, 1985] E. P. Sanders has taken a bold (though not unprecedented) and programmatic step towards making historical Jesus study intelligible, coherent and interesting. My aim here is to explore the program represented by Sanders' work and then to show how this work may actually lead to the demise of the quest of the historical Jesus.
Using Choice with Game Play to Increase Language Skills and Interactive Behaviors in Children with Autism

Children with autism often exhibit significant language delays and extremely disruptive behaviors when confronted with task situations or other interactions in which they would rather not partake. ...
Fragmentation of the universe

We have tested the hypothesis that the universe underwent a single fragmentation event, separating into protogalactic volumes at a relatively early stage after the Big Bang. Assuming that the present total luminosity of each galaxy is proportional to its mass, we plotted the number and mass distribution of a thousand nearby galaxies just as we would in an analysis of fragments from a laboratory high-explosive experiment. The results are consistent with the single-fragmentation hypothesis.
Optimal Satellite Transfers Using Relative Motion Dynamics

A first-order approximation of optimal two-burn transfers between satellite orbits within a formation is presented and discussed. The orbital transfer problem is based on the well-known fact that, to first order, such orbits are elliptic, with centers at the target or offset in the in-track direction. The methodology allows for a target in a (generally) elliptic orbit in its motion about the center of force. The solution obtained makes use of a transformation of the problem to the reference frame of an auxiliary target in circular orbit in the inertial frame. The total required |Δ v| is expressed in terms of the identifying parameters for the initial and final orbits in the formation, corresponding to their respective sizes as measured by their minor axes, location of their centers, and their orientation. This expression allows for numerical parametric studies in the case where the initial and final orbits are in the same or parallel planes. It is shown that the optimal total |Δ v| depends on the relative sizes of the orbits and the distance between their centers. When the initial and final orbits are concentric, four optimal two-burn transfers, all of the same total |Δ v|, are identified. It is further shown that the optimal |Δ v| changes with the distance between the centers of the orbits and attains a minimum when this distance is about 2.2 times the difference between the minor axes of the orbits.
The pace of rhyolite differentiation and storage in an ‘archetypical’ silicic magma system, Long Valley, California

Abstract Time scales of silicic magma processes are an important source of information pertaining to the thermal and mass fluxes through the crust but are difficult to quantify. Here we report ion microprobe 238U–206Pb ages for individual zircons from rhyolites from Long Valley caldera, California, and use these data to refine the relationship of production and storage of the 0.8–2.1 Ma precaldera Glass Mountain (GM) rhyolites to that of the caldera-related Bishop Tuff (BT) rhyolite. We also examine the timing of differentiation in the compositionally zoned BT. Most zircon crystallization in the 3 studied GM rhyolites occurred in two intervals between 2.0 and 1.7 Ma and between 1.1 and 0.85 Ma. Collectively, they support previous inferences based on Sr isotope considerations that differentiation and crystallization in silicic magmas can precede eruption by hundreds of ky. For the BT, zircons contained in the earlier, more evolved part of the eruption have U contents (mostly > 1800–4500 ppm) that are higher than those contained in the later, less evolved part of the eruption (mostly 100's to 2000 ppm). When scarce Mesozoic-aged zircons are excluded, the mean pre-eruption crystallization age for the late BT zircons studied here is about 90 ky older than a 760 ± 2 ka Ar / Ar sanidine eruption age. An identical mean pre-eruption zircon age is obtained for the early part of the BT eruption as well as in an earlier study and implies virtually simultaneous crystallization of compositionally distinct melts. Based on the largely distinct chemical and age characteristics of the zircon age populations, we conclude that the GM and BT rhyolites record episodes of punctuated and independent evolution rather than the periodic tapping of a long-lived magma chamber. Sr isotope characteristics of BT minerals previously used to support inheritance of those minerals from GM magmas can be explained by radiogenic ingrowth and by crystal growth from isotopically heterogeneous domains in the nascent BT magma chamber; evidence for the latter is provided by anomalously radiogenic feldspars.
Characterization of quinidine 3-hydroxylation as a probe for the CYP 3A enzyme using a novel capillary electrophoresis technique.

Abstract Capillary electrophoresis (CE) with a direct injection technique was used to characterize the formation of (3 S )-3-hydroxyquinidine (3-OHQ) as a probe for the CYP 3A isoenzymes in rat liver microsomes. Detection was performed either in the absorbance mode or by employing laser-induced fluorescence (LIF) detection. Michaelis–Menten parameters (mean values±S.D.) K m and V max for the formation of 3-OHQ from the probe drug quinidine sulfate (QS) in rat liver microsomes were 37±4.6 μg/ml (47.1±5.9 μM) and 321±4 ng/mg/h (942±11.7 pmol/mg/h), respectively. Inhibition studies were performed to evaluate the specificity of 3-OHQ as a probe for the CYP 3A enzyme. Ketoconazole and fluconazole were found to be inhibitors of 3-OHQ formation and exhibited K i values of 0.19 and 20.1 μM, respectively. Inhibition with the weak inhibitor, erythromycin could only be estimated using LIF detection due to lack of sensitivity in the absorbance mode. The formation of 3-OHQ in rat liver microsomes can be used as a model for the screening of the CYP 3A enzyme. Direct injection, ensures faster analysis time due to the lack of sample preparation and the low volume capabilities of the technique makes it attractive for the screening of a large number of compounds.
Connective tissue activation. XXX: Isoelectric point microheterogeneity of CTAP-III, a human platelet-derived growth factor

Connective tissue activating peptide (CTAP-III) is one of the growth factors found in the alpha granules of human platelets. This small cationic platelet protein shows several apparent isoelectric point variants after the preparative isoelectric focusing step in large scale preparations from multiple donors. Analytical isoelectricfocusing techniques under denaturing conditions, coupled with Western blotting and immunodetection, now show that CTAP-III prepared rapidly from single donors also has multiple isoelectric point variants, suggesting that this finding is more likely related to post-translational modification than preparative artifact or genetic polymorphism.
Isolation of placental and liver “mitochondrial” fractions which support steroid 11β-hydroxylation

Abstract 1. 1. Extracts of acetone powders of human placental or bovine liver “mitochondria” in the presence of bovine adrenal “mitochondrial” particles catalyze steroid 11β-hydroxylation 1 . The extracts have been subjected to (NH 4 ) 2 SO 4 fractionation, Sephadex G-100 gel filtration and DEAE-cellulose column chromatography, and fractions active in supporting 11β-hydroxylation were isolated and compared with adrenodoxin isolated from bovine adrenal “mitochondria”. 2. 2. The placental and liver DEAE-cellulose fractions did not have significant absorbence in the 400–700 nm region nor did they contain nonheme iron or acid-labile sulfur although their Chromatographic properties were similar to adrenodoxin.
Repeatability of chemical cytometry: 2-DE analysis of single RAW 264.7 macrophage cells

This report presents the use of 2-DE with ultrasensitive fluorescence detection as a chemical cytometry tool to characterize the protein and biogenic amine content of single cells from the RAW 264.7 murine macrophage cell line. Cells were sorted by cell cycle prior to 2-DE analysis. Cells in the G2/M phase of the cell cycle were aspirated into the first-dimensional capillary and lysed. The cellular contents were fluorescently labeled and first separated by capillary sieving electrophoresis (CSE). Over 380 fractions were transferred from the first-dimensional capillary to the second-dimensional capillary, where components were further separated by MEKC and detected by laser-induced fluorescence. Twenty-five spots common to the four electropherograms were fit with a 2-D Gaussian surface to determine spot position, width, and amplitude. The RSD in CSE mobility was 1.0 +/- 0.6%. The mean uncertainty in spot position was 1.3 times larger than the mean spot width in the CSE dimension. The average SD in MEKC migration time was 0.37 +/- 0.13 s, which is smaller than the average spot size in this dimension. Spot capacity was 200. The RSD in spot amplitude was 50%, reflecting a large cell-to-cell variation in component expression.
Glucocorticoid (GC)-Mediated Down-Regulation of Urokinase Plasminogen Activator Expression via the Serum and GC Regulated Kinase-1/Forkhead Box O3a Pathway

The glucocorticoid receptor (GR) and its ligand, cortisol, play a central role in human physiology. The exact mechanisms by which GR activation regulates these processes are the subject of intensive investigation. We and others have shown that GR activation can indirectly down-regulate specific genes via serum and glucocorticoid (GC) regulated kinase-1-mediated inhibition of forkhead box O3a (FOXO3a) transcriptional activity. We previously used gene expression microarrays, together with bioinformatic analyses, to identify putative FOXO3a target genes in breast epithelial cells. In this paper we refine our analysis through the use of FOXO3a chromatin immunoprecipitation (ChIP) microarrays. ChIP microarray results reveal urokinase plasminogen activator (uPA) as a putative novel target of FOXO3a in breast epithelial and breast cancer cell lines. We further show that uPA down-regulation after GC treatment requires serum and GC regulated kinase-1-mediated inactivation of FOXO3a activity. ChIP and luciferase assays confirm that FOXO3a can both occupy and transactivate the uPA promoter. Our data suggest that inactivation of FOXO3a after GR activation is an important mechanism contributing to GC-mediated repression of uPA gene expression in breast epithelial and cancer cells.
Predictors of employment in substance-using male and female welfare recipients

This study examined predictors of employment among substance-using men and women enrolled in welfare-to-work programs. Participants were 394 welfare applicants assigned to either coordinated care management or usual care for treatment services and job training and followed up for 1 year to track employment outcomes. Common barriers to work were assessed at baseline in four key domains: disabilities, situational barriers, labor capital, and motivation. Results indicated substantial gender differences in the number and profile of work barriers. Among men, work experience and job motivation were the only significant predictors of employment; among women, multiple factors from each barrier domain predicted job acquisition even when controlling for all other significant predictors. Findings suggest that welfare-to-work programs should emphasize job training and job seeking during the early stages of welfare interventions for men and for many women.
Catalytic site occupancy during ATP synthase catalysis.

An early proposal was that for rapid ATP synthesis by the rotational ATP synthase, a specific second site must bind ADP and Pi, and for rapid ATP hydrolysis a different second site must bind ATP. Such bi-site activation was considered to occur whether or not an ADP or ATP was at a third site. In contrast, a more recent proposal is that rapid ATP hydrolysis requires that all three sites have bound ADP or ATP present. However, discovery that one second site binds ADP better than ATP, together with other data and considerations support the earlier proposal. The retention or rebinding of ADP can explain why three sites fill during hydrolysis as ATP concentration is increased although bi-site activation still prevails.