cssi/SciSciGPT-SciSciNet huggingface dataset:
Gene × Environment Interactions in the Development of Preschool Effortful Control, and Its Implications for Childhood Externalizing Behavior.

This study examined the role of gene × environment interaction (G × E) in the development of effortful control (EC) and externalizing symptoms (EXT). Participants included 361 adopted children, and their Adoptive Parents (APs) and Birth Mothers (BMs), drawn from the Early Growth and Development Study. The primary adoptive caregivers’ (AP1) laxness and overreactivity were assessed when children were 27-months-old, and used as indices of environmental influences on EC. Heritable influences on child EC were assessed by the BMs’ personality characteristics (emotion dysregulation, agreeableness). Secondary adoptive caregivers (AP2) reported on children’s EC at 54 months, and EXT at 7 years. Interactions between BM characteristics and AP1 laxness were related to EC and indirectly predicted EXT via EC. Parental laxness and EC were positively associated if children had high heritable risk for poor EC (BM high emotion dysregulation or low agreeableness), but negatively associated if children had low heritable risk for poor EC (BM low emotion dysregulation or high agreeableness). BM agreeableness also moderated associations between AP1 overreactivity and effortful control, and yielded a similar pattern of results. Our findings suggest that G × E is an important first step in the development of EXT via its effect on EC. Consistent with “goodness of fit” models, heritable tendencies can affect which parenting practices best support EC development.
Cumulative Fatigue Damage Theory and Models.

This paper consists of six sections of original contributions to the theory of cumulative fatigue damage of airframe structures and a section which consists of extensive bibliography of important papers in cumulative fatigue damage. Classical models for predicting the average number of cycles-to-failure, using basically one form or another of the so-called Miner’s rule, are known to be inadequate, in the sense that they either underestimate or overestimate, in some cases, the average number of cycles-to-failure. This is because they do not take into consideration, or even do not know how to take into consideration, the various co-occurring or concomitant factors, other than the various types of loads themselves, and incorporate them into the formula for predicting the expected number of cycles-to-failure. We believe that, in this paper we have suggested methods to circumvent the drawbacks from which the classical Miner’s rule suffers, and we have also offered models, in the more difficult and realistic situation, in which the additional increments in the propagation of the dominant crack form a dependent sequence of chance variables. It is the fond hope of the authors that they and other workers in the field will have the opportunity of applying the realistic approach to predicting the average number of cycles of a large airframe, based on actual flight test data, and to compare its performance with that of methods advanced in a follow-up effort.
Characteristics of the Human Lymphocyte Insulin Receptor

Abstract Insulin interactions with human lymphocytes in established cultures and with isolated peripheral lymphocytes have been studied using 125I-insulin. Receptors in circulating lymphocytes are indistinguishable from those found in cultured cells, and the lymphocyte receptors show striking similarities to those structures described in fat cell and liver preparations. In lymphocytes, the ability of insulin or insulin analogues to inhibit binding of 125I-insulin is directly proportional to the ability of that preparation to inhibit binding of labeled hormone to purified liver membranes or to stimulate glucose oxidation in the fat cell. Binding of 125I-insulin to lymphocytes is a rapid and reversible process. Binding is maximal at 15°. Dissociation rate studies revealed a biphasic curve and the constants obtained were 8.3 x 10-5 s-1 and 8.3 x 10-4 s-1. The apparent affinity constants of the two orders of binding sites in the cultured lymphocytes were 1.2 x 1010 m-1 and 1.1 x 109 m-1, whereas in the normal circulating lymphocytes the values were 2.0 x 109 m-1 and 1.4 x 108 m-1. At 30° there is very little degradation of labeled insulin by lymphocytes, and at 15° there is no detectable degradation with cultured or circulating cells. Binding of 125I-insulin to cultured lymphocytes is unaffected by Ca++, Mg++, or EDTA. The optimum pH for binding occurs at about 7.8. Insulin binding to cells is unaffected by digestion with DNase, RNase, or neuraminidase. However, tryptic digestion destroys the capacity of the cells to bind insulin.
Fatty Acid Distribution in Mesophilic and Thermophilic Strains of the Genus Bacillus

The fatty acid distribution of three mesophilic and three thermophilic strains of the genus Bacillus was determined by gas chromatography of the fatty acid methyl esters. Fatty acid i-15:0 was the most abundant in both the mesophiles (51%) and the thermophiles (41%). The second most abundant fatty acid was a-15:0 in the mesophiles (22%), and i-17:0 in the thermophiles (27%). The fatty acid pair i-15:0, i-17:0 was the most predominant pair in both the mesophiles (61%) and the thermophiles (66%). The fatty acid pair a-15:0, a-17:0 was the second most predominant pair and was much higher in the mesophiles (30%) than in the thermophiles (15%). The average fatty acid chain length was 15.5 for the mesophiles and 16.0 for the thermophiles. The significance of these results for the lipid theory of thermophily is discussed.
Columns and Beams Braced by Diaphragms

Shear-resistant light-gage metal diaphragms, such as wall cladding, roof decking, and floor panels, often are connected directly to beams or columns of a steel framework. Using an energy approach, analytical methods are developed for predicting the buckling strength of individual diaphragm-braced I-section members in the plane of the diaphragm. Sixteen tests of centrally loaded double-column assemblies with diaphragm bracing on one or both flanges, and eight tests of double-beam assemblies with diaphragm bracing on the compression flange, give satisfactory agreement with theoretical results. Theory and test results both indicate that shear-resistant diaphragms can be effective in increasing the buckling load of slender columns and beams.
One Possible Frame for Thinking about Experiential Learning

Summary I argue that teaching statistical thinking is harder than teaching mathematics, that experimental design is particularly well suited to teaching statistical thinking and that in teaching statistics, variation is good. We need a mix of archival data, simulations and activities, of varying degrees of complexity. Within this context, I applaud the important contributions to our profession represented by Darius et al. (2007), and Nolan & Temple Lang (2007), the first for showing us how to make simulation-based learning simultaneously more flexible and more realistic than ever before, and the second for showing us a path-breaking technology that can make archival data the basis for active learning at an impressively high level of sophistication, embedding statistical thinking within real scientific and practical investigations.
Interactions during a critical period inhibit bilateral projections in embryonic neurons

The anterior pagoda (AP) neurons in the CNS of the medicinal leech are found as homologous pairs in 20 of the 21 midbody ganglia. Each AP is the mirror image of its mate, extending its main axon across the midline of the CNS and eventually into the contralateral body wall, thereby attaining a unilateral pattern of innervation. Certain features of the adult AP morphology are known to arise through interactions among homologs early in development (Gao and Macagno, 1987b), but it is not known whether the contralateral nature of the projection pattern is due to intrinsic “one-sidedness” or rather to cell-cell interactions that inhibit the formation of a second, ipsilateral projection. In the experiments described in this report, we tested the possibility that an AP's contralateral homolog itself inhibits the formation of bilateral projections. One AP was photoablated in the intact embryo early in development and then the response of the remaining AP was examined. We found that an AP can extend bilaterally symmetrical projections when its homolog is missing, but only during a critical period that, interestingly, begins when an AP's interactions with other specific neurons come to an end. To determine whether synaptic communication between AP homologs could be responsible for the timing of this critical period, we recorded electrophysiologically from pairs of embryonic AP neurons. Although no detectable chemical signaling was observed, AP cells were electrically coupled throughout the entire critical period. Further, the junctions between these neurons were permeated by 5-HT, whereas larger molecules such as carboxyfluorescein were impermeant. This dye coupling decreased with age even while electrical coupling persisted, suggesting but not proving that the properties of the gap junctions between AP neurons may also change with time. We conclude that unilateral AP cells possess the intrinsic ability to project bilaterally, but are inhibited from doing so by age- dependent interactions with homologous neurons, possibly mediated by gap-junctional communication.
The arrow-tipped loop is a marker of radiculomedullary vein thrombosis linked to the anti-reflux mechanism--angiographic anatomy and clinical implications.

Introduction This article proposes that the “arrow-tipped” loop or anastomosis classically described as an anatomic variant represents in fact a pathological phenomenon resulting from the partial thrombosis of a radiculomedullary vein (RMV) with a duplicated origin (double-rooted RMVs). Methods Thearrow-tip loopconcept proposedinthisreportis illustrated with angiographic observations of patients with underlying pathologies of the spinal venous system, three cases of spinal arteriovenous fistulas, and one case of spinal venous insufficiency. Results In each clinical case, the presence of arrow-tip loops was associated with diffuse alteration of the perimedullary venous system, including the lack of detectable RMVs. The angiographic appearance of the arrow-tip loops suggested partially thrombosed double-rooted RMVs, with rootlets originating either from the anterior or posterior spinal veins, or from both. Conclusion While a thrombosed single-rooted RMV typically becomes anatomically and angiographically undetectable, double-rooted MRVs keep a flowing proximal segment made of their two rootlets of origin. This residual proximal segment takes the appearance of an arrow-tip loop, which therefore be seen as an indicator of spinal venous thrombosis.
Off-balance-sheet credit risk of the top 20 Japanese banks

The study of off-balance-sheet (OBS) credit risk across the top 20 Japanese banks indicated that financial derivatives were heavily used by the top four banks and that loan commitments are the largest source of credit risk among traditional OBS instruments. The notional amounts of derivative contracts make up 92 per cent of total OBS activities. There is a wide difference across the banks in the use of derivative leverage. As compared to the US and European banks, Japanese banks use fewer OBS instruments as a percentage of their assets. This implies that Japanese banks are more conservative and risk averse in general than their US or European counterparts, especially given the bad financial condition of the banks and Japan.
Effects of Fumagillin and Thalidomide Treatment on Alveolarization in the Developing Rat Lung

Effects of Fumagillin and Thalidomide Treatment on Alveolarization in the Developing Rat Lung
Rate and extent of decline in Corallium (pink and red coral) populations: existing data meet the requirements for a CITES Appendix II listing

In June 2007, the US government proposed Corallium (pink and red corals) for listing on Appendix II of the Convention on International Trade in Endangered Species (CITES). The proposal was adopted and later overturned due to perceived difficulties in implementing and enforcing a CITES listing and uncertainties on population status. An expert review (Food and Agriculture Orga- nization) questioned whether populations had declined to 20-30% of the historic baseline, the level required for a CITES Appendix II listing. This review used colony abundance and density as surro- gates of decline, which may be high (200 to 1300 colonies m -2 ) in the Mediterranean. Yet assessments of decline for colonial organisms should also consider changes in size, since reproductive output and survival increase exponentially with size. Colonies of C. rubrum historically achieved heights of 50 cm with complex first, second and third order branching patterns. Today, >90% of colonies in fished areas are 3 to 5 cm tall, <50% are sexually mature and most have only rudimentary branches. Few population data are available for Pacific Corallium spp.; however, landings over the last 15 yr have declined from 100-400 to <5 t yr -1 . Recovery of populations to their natural state may require decades, as colonies in protected areas are less than half their historic size after 20 to 30 yr of protection. Mini- mum allowable size for harvest should be increased because traditionally determined growth rates appear to underestimate colony age, and corals are being removed long before achieving maximum sustainable yield. 'Boom and bust' cycles of Corallium fisheries and dramatic, long-lasting shifts in population demography highlight the need for improved management and trade regulations.
Separation for childbirth: The effect on the sibling

The reactions of 14 young (one to three and one-half years) first born children to the routine two to six day separation associated with maternal childbirth were compared with 17 children permitted to visit their mothers in hospital for one hour per day. Behavior observations in the home one to two weeks after birth compared to those made two to four weeks before birth as well as maternal questionnaires revealed significant increases in tekmper tantrums, excessive activity and sleep problems in both groups. Children, however, who sisited were initially significantly more responsive to their mothers and new siblings.
A Short Synthesis of Symmetrical Betweenanemes

Abstract In the course of studies on the synthesis and chemistry of betweenanenes1 we have devised a short route (Chart I) to symmetrical members of the family (e.g., 4) which we disclose herewith.
Classification of background noises for hearing‐aid applications

A background-noise classification procedure is being developed for hearing-aid applications, wherein the hearing-aid response would be adjusted in response to changes in the noise environment. The classification procedure is based on measuring four signal features giving the fluctuations of the signal envelope and the mean frequency and low- and high-frequency slopes of the average spectrum. A more complicated procedure, based on determining the envelope modulation spectra in auditory critical bands, was also investigated and was found to offer no advantages over the simpler procedure. The accuracy of the classification procedure was determined for eleven everyday background noises under optimal conditions where the training and test noise sequences were different portions of the same short noise recording. A cluster analysis was used to determine the similarities among the feature vectors for the noises, and when the noises are grouped into a reduced number of clusters the noise-classification accuracy using the four features exceeds 90%.
Women's organisations seeking gender justice in the Sudan 1964-1985

The Sudan had a multiple legal system governing various aspects of its people's lives, however Shar`ia has been applied consistently to family law. Shar`ia, Muslim's interpretation of religious norms expressed in the Qura'n and Sunna, differed according to the time and place of application. This article compares two women's groups, the Sudanese Women's Union and the Republican Sisters, discussing the factors that shaped their methods and conceptualisation of their quest to seek gender justice without losing religious legitimacy. The Republican Sisters proved that a reinterpretation of Islamic norms can be advocated by a religious group, and not just by secular ones. The political and social climate had, and continues to have, a significant effect on the laws and the ways women react to their suppression in the name of religion.
Ability of blind people to detect obstacles in unfamiliar environments.

Purpose: To describe obstacle detection, sometimes called face vision, and blind peoples' lived experiences. Design: This Husserlian phenomenologic inquiry included a convenience sample of eight blind participants who possessed the ability to detect obstacles in unfamiliar environments. Methods: Face-to-face conversations were audiotaped in a setting of the participant's choice. Findings: Three themes were identified: “a sense that something is there,”“sensing,” and “space.” These three entwined themes were recognized in the unity-of-meaning or uniting theme: sensing presence as open or closed space. Conclusions: The findings of this study indicate many questions for nurses. Given the synergistic recognition of obstacles that the participants described, secondary analysis of the data is indicated, for example regarding pattern recognition and human environmental field integrality.
Contra: 'Warfarin should be the drug of choice for thromboprophylaxis in elderly patients with atrial fibrillation' - Caveats regarding use of oral anticoagulant therapy among elderly patients with atrial fibrillation

Contra: 'Warfarin should be the drug of choice for thromboprophylaxis in elderly patients with atrial fibrillation' - Caveats regarding use of oral anticoagulant therapy among elderly patients with atrial fibrillation -
Interaction and Regulation of Subcellular Localization of CED-4 by CED-9

The Caenorhabditis elegans survival gene ced-9 regulates ced-4 activity and inhibits cell death, but the mechanism by which this occurs is unknown. Through a genetic screen for CED-4-binding proteins, CED-9 was identified as an interacting partner of CED-4. CED-9, but not loss-of-function mutants, associated specifically with CED-4 in yeast or mammalian cells. The CED-9 protein localized primarily to intracellular membranes and the perinuclear region, whereas CED-4 was distributed in the cytosol. Expression of CED-9, but not a mutant lacking the carboxy-terminal hydrophobic domain, targeted CED-4 from the cytosol to intracellular membranes in mammalian cells. Thus, the actions of CED-4 and CED-9 are directly linked, which could provide the basis for the regulation of programmed cell death in C. elegans.
Realizing Carbon's Value: Discourse and Calculation in the Production of Carbon Forestry Offsets in Costa Rica

: This article examines the relation between discourse and value in the production of a carbon forestry offset project among indigenous smallholders in Costa Rica. By analyzing a pivotal cost–benefit calculation that changed the trajectory of the project, this article makes two principal claims. First, the intelligibility of the calculation is grounded in a discursive formation that is emergent from a history of development projects in the region, where particular ways of speaking about the relation between indigenous bodies and agriculture have allowed carbon's commodification to emerge as a desirable project. Second, the calculations resulted in quantified representations of space that were necessary for the offset to become useful within the framework of the Kyoto Protocol. In this case, the forestry offset's use value derived from quantified representations of agricultural space; a process that opened some forms of land use for receiving carbon while foreclosing on others.
Exchange between free- and phospholipidalcoholic amines in microsomal membranes of Acanthamoeba palestinensis.

Cell-free extracts of the soil amoeba Acanthamoeba palestinensis have been found to catalyze the incorporation of choline, L-serine and ethanolamine into phospholipids of intracellular membranes in the presence of Ca2+ and the absence of other exogenous factors. Cell fractions enriched in endoplasmic reticulum and mitochondria contained the highest activity, while plasma membranes demonstrated no activity. Microsomal pellets were used to characterize the enzyme activity. Mg2+ could not replace Ca2+, but did not inhibit Ca2+-dependent activity, while Mn2+ inhibited activity. Choline incorporation was competitively inhibited by L-serine and less effectively by ethanolamine. L-Serine incorporation was competitively inhibited by ethanolamine and inhibited by choline only at low concentrations. Ethanolamine incorporation was competitively inhibited by L-serine, while choline had no inhibitory effects. The specificities of the competitive inhibition of incorporation of each alcoholic amine indicated that more than one enzyme or enzymatic site was involved and that incorporation occurred via a direct base exchange mechanism.Inactivation of incorporation enzymes occurred in an exponential fashion during incubation of microsomal membranes at 29° in the presence of Ca2+. However, the measured rates of inactivation could not account for the low levels of incorporation experimentally observed with each of the three alcoholic amines. Quantitative analysis of the turnover of radioactive bases of prelabeled phospholipids predicted ongoing loss of the labeled bases from phospholipids that was not due to exchange, as well as the unavailability of a constantly increasing fraction of the labeled bases for such loss and/or exchange.
Bus Selection in Multibus DC Microgrids

DC power systems can be made more reliable by using multiple buses for redundancy. Multiple buses provide multiple configuration options for supplying power to the load. Diode OR'ing with auctioneering diodes is perhaps the most common method to connect a load to multiple buses. Although the diode action is automatic and fault-tolerant, it results in ill-defined bus currents when the bus voltages are similar and the potential for uncontrolled switching in a faulted high-impedance system-operating scenarios not often included in a discussion on auctioneering diodes. Active switching and bus converters with auctioneering diodes are control techniques that overcome these limitations by providing full control over the bus selection process. Using local information in the form of the bus voltage, these techniques do not rely on a centralized controller, which improves system reliability. Dwell time is proposed as a technique to stabilize the state-dependent switching in the bus selector.
Shade-grown cacao supports a self-sustaining population of two-toed but not three-toed sloths

Summary The development of shade-grown agro-ecosystems has increasingly been identified as a strategy for conserving tropical biodiversity. While biodiversity tends to be higher in agro-ecosystems than in monocultures, the extent to which shade-grown crops support viable populations of sensitive and specialized tropical species has not been assessed. We conducted a comparative demographic study between Hoffmann's two-toed sloth Choloepus hoffmanni and the brown-throated three-toed sloth Bradypus variegatus in a shade-grown cacao farm in Costa Rica. Choloepus hoffmanni bred year-round, whereas B. variegatus bred seasonally, with females giving birth to young over a 6-month period peaking in late February. Relatively short time to offspring independence allowed B. variegatus females to breed annually, but longer periods of maternal care prevented C. hoffmanni from doing so. Annual survival rates for adult males of both species derived from radiomarking and known fates models were high (>0·90). Most adult mortality was the result of predation by domestic dogs Canis lupus familiaris and coyotes Canis latrans. Estimates of population growth rates derived from a matrix population model indicated that the abundance of C. hoffmanni, but not B. variegatus, was stable in the absence of immigration. However, genetic parentage methods indicated that significant immigration of B. variegatus into the study area occurred and that the local population may be stable. Synthesis and applications. Our results suggest that shade-grown crops embedded within an agro-ecosystem can support viable populations of some specialized tropical animals; other species, however, may require immigration from surrounding forests to maintain stable populations. More broadly, the value of human-modified landscapes for biodiversity may be overestimated when some species are dependent on immigration from intact habitats.
Nodular regenerative hyperplasia of the liver following bone marrow transplantation

Liver disease in the early period following bone marrow transplantation may be due to a number of causes, including pretransplant cytoreduction with chemotherapy and irradiation. Although the relationship of venoocclusive disease to these agents has been well established, another process, nodular regenerative hyperplasia, may also occur. In this retrospective study, we evaluated the incidence and clinical signs of these two processes as defined by histological criteria. In 103 patients studied, nine (8.8%) had venoocclusive disease and 23 (22.5%) had nodular regenerative hyperplasia. Venoocclusive disease was significantly associated with transplantation for malignancy other than acute or chronic leukemia and use of busulfan as a cytoreductive agent and occurred in younger patients. Nodular regenerative hyperplasia did not differ from the general transplant population in terms of underlying disease, cytoreductive regimen, graft vs. host disease prophylaxis or age. Both venoocclusive disease and nodular regenerative hyperplasia were associated with ascites. Venoocclusive disease had a poor prognosis, with eight of nine cases dying of or with venoocclusive disease, whereas no case of nodular regenerative hyperplasia died of liver disease and only 5 of 23 died with nodular regenerative hyperplasia. Using retrospective data, five of 11 patients fulfilling clinical criteria for the diagnosis of venoocclusive disease actually had nodular regenerative hyperplasia, as did all of nine patients fulfilling the criteria for "possible" venoocclusive disease. These results indicate that nodular regenerative hyperplasia is a process which occurs commonly following bone marrow transplantation and which may be clinically misdiagnosed as venoocclusive disease.
Detecting natural abundance carbon signal of NAA metabolite within 12-cm3 localized volume of human brain using 1H-[13C] NMR spectroscopy.

NMR spectroscopy has been applied extensively to study metabolism noninvasively in the human brain and other tissues. However, it usually suffers from poor signal-to-noise ratio due to low NMR sensitivity and low metabolite concentrations. In this study, the technique of proton-observe- carbon-edited (POCE) NMR spectroscopy combined with a single-shot localization sequence was used to detect the natural abundance carbon signal of the amino acid N-acetyl aspartate from a 12-cm3 localized volume in the occipital lobe of humans at 4 T. The results suggest that NMR spectroscopy is sensitive enough to detect signals from low concentration metabolites (<60 nmol/g) from small volumes in the human brain within several minutes of data acquisition. This reveals that in vivo NMR spectroscopy is a promising technique for detecting small metabolite changes and low traces of 13C isotopic labeling for dynamic metabolism studies aimed at investigating physiological and pathological questions.
Development of a human immunodeficiency virus-1 in vitro DNA synthesis system to study reverse transcriptase inhibitors

A Human immunodeficiency virus type-1 endogenous reverse transcriptase reaction was developed as an in vitro assay to study the inhibition of reverse transcription by antiviral compounds. Conditions were established for producing genomic length (-) strand DNA in high yields and measuring the inhibition of this transcript as the assay endpoint. In addition to genomic length (-) strand DNA, a novel segmented (-) strand product composed of a 6.0 kb reverse transcript of the 5' 2/3 of the viral RNA genome and a 3.5 kb reverse transcript of the 3' 1/3 was observed. The most prominent (+) strand product was the size expected for plus-strong stop DNA. Additional minor (+) strand species were also observed. The triphosphate form of the nucleoside analog inhibitor 3'-azido-3'-deoxythymidine (RETROVIR, Zidovudine, AZT) and BI-RG-587 (nevirapine), a non nucleoside inhibitor, were used to demonstrate the utility of the endogenous system for the analysis of reverse transcriptase inhibitors. In a standard reaction, synthesis of genomic length DNA was 50% inhibited by 0.1 microM AZTTP and 0.1 microM nevirapine.
Generation of nanoparticle agglomerates and their dispersion in lung serum simulant or water

Nanoparticles released into the atmosphere, due to their high diffusivity, will likely begin to agglomerate. The state of agglomeration upon inhalation and the potential to disperse back into nanoparticles may affect the toxicity of the inhaled material. In order to investigate particle dispersion, a system was set up to generate aggregates from agglomerates. Primary particles, composed of zinc, were generated using zinc rods in a spark generator (Palas GFG-1000, Karlsrhue, Germany). These particles formed agglomerates which were passed through a room temperature aging chamber or through a tube furnace (Carbolite HST, Derbyshire, UK). Agglomerate size was measured with a scanning mobility particle sizer (SMPS model 3936, TSI Inc., Shoreview, MN). When furnace temperature was set near the zinc coalescence temperature, instead of decreasing in size, agglomerate size increased up to 30%; a percentage increase duplicated with the room temperature aging chamber. Starting with an aerosol of primary zinc particles, equal concentrations of agglomerate and aggregrate aerosol were produced. The extent of breakup and dispersion of agglomerates and aggregates to individual nanoparticles in lung serum simulant will be assessed using transmission electron microscopy.
Borrowing from tobacco control to curtail the overweight and obesity epidemic: Leveraging the U.S. Surgeon General's Report

There is broad agreement that more needs to be done to curtail the U.S. overweight and obesity epidemic. Fifty years of regular Surgeon General's Reports on the health consequences of smoking appear to have been a highly effective contributor to the notable successes that have been made in reducing smoking prevalence. Comparing the rate of Surgeon General's Reports on smoking and obesity reveals striking differences, with more than a five-fold lower rate of reporting on the latter. Developing practices that more effectively leverage the power of the U.S. Surgeon General's Office in efforts to reduce obesity is a relatively straightforward but potentially powerful additional step that warrants consideration.
Defects in Mitochondrial Dynamics and Metabolomic Signatures of Evolving Energetic Stress in Mouse Models of Familial Alzheimer's Disease

Background The identification of early mechanisms underlying Alzheimer's Disease (AD) and associated biomarkers could advance development of new therapies and improve monitoring and predicting of AD progression. Mitochondrial dysfunction has been suggested to underlie AD pathophysiology, however, no comprehensive study exists that evaluates the effect of different familial AD (FAD) mutations on mitochondrial function, dynamics, and brain energetics. Methods and Findings We characterized early mitochondrial dysfunction and metabolomic signatures of energetic stress in three commonly used transgenic mouse models of FAD. Assessment of mitochondrial motility, distribution, dynamics, morphology, and metabolomic profiling revealed the specific effect of each FAD mutation on the development of mitochondrial stress and dysfunction. Inhibition of mitochondrial trafficking was characteristic for embryonic neurons from mice expressing mutant human presenilin 1, PS1(M146L) and the double mutation of human amyloid precursor protein APP(Tg2576) and PS1(M146L) contributing to the increased susceptibility of neurons to excitotoxic cell death. Significant changes in mitochondrial morphology were detected in APP and APP/PS1 mice. All three FAD models demonstrated a loss of the integrity of synaptic mitochondria and energy production. Metabolomic profiling revealed mutation-specific changes in the levels of metabolites reflecting altered energy metabolism and mitochondrial dysfunction in brains of FAD mice. Metabolic biomarkers adequately reflected gender differences similar to that reported for AD patients and correlated well with the biomarkers currently used for diagnosis in humans. Conclusions Mutation-specific alterations in mitochondrial dynamics, morphology and function in FAD mice occurred prior to the onset of memory and neurological phenotype and before the formation of amyloid deposits. Metabolomic signatures of mitochondrial stress and altered energy metabolism indicated alterations in nucleotide, Krebs cycle, energy transfer, carbohydrate, neurotransmitter, and amino acid metabolic pathways. Mitochondrial dysfunction, therefore, is an underlying event in AD progression, and FAD mouse models provide valuable tools to study early molecular mechanisms implicated in AD.
A phase I study of cetuximab/paclitaxel in patients with advanced-stage breast cancer.

Abstract Background The epidermal growth factor receptor (EGFR) is part of the ErbB family of receptor tyrosine kinases and is known to be variably expressed in breast cancers. Cetuximab is a humanized monoclonal antibody directed against the EGFR that works by blocking the downstream signaling function of this protein and thereby interfering with cancer cell proliferation. Preclinical studies have indicated a synergistic effect for the combination of anti-EGFR therapy plus paclitaxel in breast cancer models. Patients and Methods Hence, we conducted a dose-escalation phase I trial using cetuximab/paclitaxel in patients with metastatic breast cancer to evaluate the feasibility of this combination. Patients with EGFR-positive metastatic breast cancer treated with=1 previous therapy, excluding taxanes, were eligible. Treatment consisted of weekly cetuximab therapy and every-3-week paclitaxel, with dose escalation of cetuximab until the maximum tolerated dose was reached. Results Twelve patients were enrolled to 3 treatment cohorts. Two of 6 patients on the second cohort (cetuximab 100 mg/m 2 ) developed dose-limiting toxicities, presenting as grade 3 rash. The third cohort was amended to allow the same cetuximab dose but to modify the paclitaxel to a weekly schedule. Despite this, 1 of 3 patients in this group also developed grade 3 skin toxicity as a dose-limiting toxicity; thus, the trial was stopped. Ten of the 12 patients were evaluable for response, and of these, 2 patients experienced stable disease, and 8 patients experienced disease progression. Conclusion Because of prohibitive dermatologic toxicity and disappointing preliminary efficacy, the combination of paclitaxel/cetuximab was not considered promising in this population, although further study of this regimen might be warranted.
Oral Bisphosphonate Prescriptions and the Risk of Esophageal Adenocarcinoma in Patients with Barrett’s Esophagus

Background Recent case reports suggested a link between oral bisphosphonate use and esophageal cancer. We therefore examined the association between these medications and the risk of esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus (BE).
Recurrent falls, warfarin doses and pharmacogenetics, pharmacist care

Recurrent falls Falls are associated with medications with substantial central nervous system (CNS) complications among older patients. Joseph T Hanlon, PharmD, University of Pittsburgh, and colleagues examined the association between recurrent falls (two or more) and time-varying exposure to CNS medications.1 The authors studied 3,055 older patients (70–79 years) with no functional limitations at baseline. Interviews were conducted annually for 6 years. Patients’ CNS medications (e.g., benzodiazepines opioid receptor agonists, antipsychotics, antidepressants) and the number of falls during the year were noted by trained interviewers. The standardized daily dose (SDD) for these medications was classified as low ( 3.0 SDD). Model estimates took advantage of the time-varying exposure strength. At baseline, 6.1% of patients reported recurrent falls; the rate was 9.7% in year 6. Compared with patients taking no CNS medications, those with moderate (odds ratio 1.80 [95% CI 1.31–2.47]) and high (2.89 [1.96–4.25]) SDD values were more likely to have recurrent falls. Conclusion. Health professionals must be cautious with older patients taking medications with CNS effects because of their cumulative effect and consider reducing psychoactive medications whenever possible.
Kinematics of the Nucleus of NGC 1275 (3C 84)

We have used the NRAO Very Long Baseline Array to image the nucleus of NGC 1275 (3C 84) at frequencies of 15 and 43 GHz, with an angular resolution of about 0.6 and 0.15 mas, respectively. On scales of 0.05-5 pc (0.15-15 mas), the previously identified regions of radio emission are seen with unprecedented clarity: a bright and complex central core, a southern cocoon-like "expanding bubble," a faint, thin jet connecting the core to the bubble, and an inverted spectrum northern "counterfeature." The inner 0.5 pc of the core has bright knots of emission located along a line with multiple sharp bends, as if sprayed from a precessing nozzle with a full opening angle of ~40°. These knots move at 0.05c, 0.08c, and 0.2c (±0.03c), for components at increasing distances from the core, indicative of acceleration along the jet. However, there are rapid and progressive flux changes in the slow-moving knots, corresponding to a phase velocity of ~0.9c±0.1c.
The long way toward multivariate predictive control of flotation processes

Abstract Flotation processes are very complex, and after more than one hundred years of history, there are few reports on applications of novel techniques in monitoring and control of flotation units, circuits and global plants. On the other hand, the successful application of multivariate predictive control on other processes is well known. In this paper, an analysis on how the characteristics of flotation processes, the quality of measurements of key variables, and the general lack of realistic dynamic models, are delaying the appropriate use of predictive control. In this context, the applications of multivariate statistics, such as PCA, to model the relationship between operating data for on-line diagnosis and fault detection and to build causal models are discussed. Also the use of PLS models to predict target variables for control purposes, is presented. Results, obtained at pilot and industrial scales, are discussed, introducing new ideas on how to obtain more valuable information from the usual available operating data of the plant, and particularly from froth images.
Symbol timing estimation in MIMO correlated flat-fading channels

Summary In this paper, the data aided (DA) and non-data aided (NDA) maximum likelihood (ML) symbol timing estimators and their corresponding conditional Cramer–Rao bound (CCRB) and modified Cramer–Rao bound (MCRB) in multiple-input-multiple-output (MIMO) correlated flat-fading channels are derived. It is shown that the approximated ML algorithm in References [4,13] is just a special case of the DA ML estimator; while the extended squaring algorithm in Reference [14] is just a special case of the NDA ML estimator. For the DA case, the optimal orthogonal training sequences are also derived. It is found that the optimal orthogonal sequences resemble the Walsh sequences, but present different envelopes. Simulation results under different operating conditions (e.g. number of antennas and correlation between antennas) are given to assess and compare the performances of the DA and NDA ML estimators with respect to their corresponding CCRBs and MCRBs. It is found that (i) the mean square error (MSE) of the DA ML estimator is close to the CCRB and MCRB, (ii) the MSE of the NDA ML estimator is close to the CCRB but not to the MCRB, (iii) the MSEs of both DA and NDA ML estimators are approximately independent of the number of transmit antennas and are inversely proportional to the number of receive antennas, (iv) correlation between antennas has little effect on the MSEs of DA and NDA ML estimators and (v) DA ML estimator performs better than NDA ML estimator at the cost of lower transmission efficiency and higher implementation complexity. Copyright # 2004 John Wiley & Sons, Ltd.
A Case of Relapsed Down Syndrome–Associated Acute Megakaryoblastic Leukemia Cured with Non-Myeloablative Chemotherapy

Abstract Despite the excellent prognosis for patients with newly diagnosed Down syndrome–associated acute megakaryoblastic leukemia (DS-AMKL), patients with relapsed DS-AMKL have very poor prognosis, and there is no standard treatment for such patients. We report a case of a child with relapsed DS-AMKL who was cured with non-myeloablative chemotherapy. A 19-month-old boy with Down syndrome, who had transient leukemia as a newborn, developed DS-AMKL (positive for GATA1 mutation), after a brief phase of myelodysplastic syndrome. He was treated with cytarabine, daunorubicin, oral thioguanine, and intrathecal cytarabine for induction; and high-dose cytarabine plus L-asparaginase and intrathecal cytarabine for intensification and consolidation. He exhibited remission but relapsed within 6 weeks after the completion of therapy. A second remission was achieved with high-dose cytarabine plus mitoxantrone (HAM), after which he received 4 more cycles of chemotherapy: 1 course of HAM; 1 course of high-dose cytarabine; and 2 courses of cytarabine, fludarabine, and granulocyte colony-stimulating factor. He has been disease-free for 65 months after the completion of chemotherapy. His bone marrow aspirate became negative for GATA1 mutation after the fourth cycle of chemotherapy, and he has remained negative at 5, 7, and 8 months after completion of therapy. A non-myeloablative chemotherapy regimen with high-dose cytarabine, mitoxantrone, and fludarabine could be curative for children with DS-AMKL.
Radiogenic and stable isotope studies of hot-spring deposits in Yellowstone National Park and their genetic implications.

Samples of travertine and siliceous sinter from hot-spring deposits in Yellowstone National Park of northwestern Wyoming have been analyzed for light stable (carbon and oxygen) and radiogenic (lead and strontium) isotopes. The Hillside Springs travertine contains significantly lighter δ13C than the previously studied Mammoth travertine. Although this relation could indicate a component of magmatic carbon, more likely it reflects a higher temperature of precipitation for Hillside Spring travertine. Our data on Mammoth travertine shows it to have been precipitated substantially below the orifice temperature. The oxygen isotope data on the newly analyzed deposits confirm the previous studies that found the hot-spring waters to be dominated by meteoric water. The lead isotope data show that there is a sedimentary component of lead in all the hot-spring deposits analyzed, including those inside the caldera limits. Either long lateral migration of waters are involved in the recharge of the springs or there must be sediments buried at some unknown depth beneath the volcanic rocks inside the caldera because no sediments are known at the surface. The high rainfall inside the limits of the caldera would favor sediments buried at depth.
Realist Visions of the End of the Cold War: Morgenthau, Aron and Waltz

Although realist theory did not predict the end of the cold war, prominent realist scholars such as Hans Morgenthau, Raymond Aron and Kenneth Waltz did give some thought to the conditions under which the cold war might be settled. Both Aron and Morgenthau characterised the cold war as a combination of traditional power politics and ideological competition, but they differed on the relative weight of each component. For Morgenthau, a diplomatic settlement would deactivate the unsettling potential of the ideological conflict; for Aron, only the disappearance of the ideological conflict could pave the way to some lasting diplomatic settlement. For Waltz, ideology had little impact; the bipolar structure of the international system was the main variable on which both the cold war and its end depended.
Mobilizing local resources in developing countries

Many developing countries are putting increased pressure on local governments to mobilize resources, especially to meet the recurrent costs of operating and maintaining locally sited capital projects. Local taxes, user charges and voluntary contributions are all possible mechanisms to carry out these efforts. Yet several important issues arise whenever these mobilization instruments are contemplated and evaluated. Several, often competing, objectives must be considered when evaluating fiscal instruments including the ability of the mechanism to raise revenues, its effect on economic efficiency, its equity implications and its administrative feasibility. After discussing each of these objectives, we show how numerous constraints, including those imposed by the political/legal system, administrative structure, the economy and the culture of the country, must be recognized while searching for a workable set of reforms that will mobilize additional resources without doing great harm to the other objectives. The key to these reforms would seem to be incentives or disincentives inherent in the revenue structure. Without recognizing these incentives or attempting to alter them, resource mobilization efforts are likely to go astray.
Sexual Maturity as Determined from Ovum Diameters in Striped Bass from North Carolina

Abstract Sexual maturity of striped bass, Roccus saxatilis (Walbaum), was investigated in the Albemarle Sound-Roanoke River system of North Carolina during the periods October 1956 through January 1957, October 1957 through April 1958, and April through September 1960. A method which permitted the determination of maturity through the measurement of ova was used. Percentages of mature female fish during several months prior to spawning are given by age group. At age-group VII and older, there was evidence of intermittent spawning and the possibility of cessation.
Detectability of phenols and amines by normal phase microbore HPLC-FTIR employing hihgly IR transparent solvents

Several chromatographic parameters have been examined as to their effect on detectability for microbore high-performance liquid chromatography coupled with Fourier-transform infrared spectrometry. Detection limits for several compound classes are presented as amount injected. Improvements in detectability for this technique are discussed.
Advances in atomic force microscopy

This article reviews the progress of atomic force microscopy in ultrahigh vacuum, starting with its invention and covering most of the recent developments. Today, dynamic force microscopy allows us to image surfaces of conductors and insulators in vacuum with atomic resolution. The most widely used technique for atomic-resolution force microscopy in vacuum is frequency-modulation atomic force microscopy (FM-AFM). This technique, as well as other dynamic methods, is explained in detail in this article. In the last few years many groups have expanded the empirical knowledge and deepened our theoretical understanding of frequency-modulation atomic force microscopy. Consequently spatial resolution and ease of use have been increased dramatically. Vacuum atomic force microscopy opens up new classes of experiments, ranging from imaging of insulators with true atomic resolution to the measurement of forces between individual atoms.