cssi/SciSciGPT-SciSciNet huggingface dataset:
Brain, plasma and tissue pharmacokinetics of risperidone and 9-hydroxyrisperidone after separate oral administration to rats

Rationale: Following an oral dose of risperidone (RSP), concentrations of its major metabolite 9-hydroxyrisperidone (9-OHRSP) were high in plasma and tissues but disproportionately lower in the brain compared to RSP, indicating that 9-OHRSP may have different pharmacokinetic properties. Objectives: To investigate non-compartmental pharmacokinetics of RSP and 9-OHRSP in plasma, brain and other tissues after separate administration of a single oral dose of 6 mg/kg RSP and 9-OHRSP to rats. Methods: Plasma, brain, liver, lung, kidney and spleen tissues were collected at pre-dose and at 0.5, 1, 2, 5, 6, 12, 24, 36 and 48 h post-dose, homogenized in saline and assayed for RSP and 9-OHRSP using a sensitive and specific liquid chromatography tandem mass spectrometry method. Results: The concentration-time curve of RSP and 9-OHRSP showed that they were readily absorbed and followed a multiphase elimination pattern. The terminal elimination half-life (\(\)\(t_{{\raise0.7ex\hbox{$1$} \!\mathord{\left/ {\vphantom {1 2}}\right.\kern-\nulldelimiterspace} \!\lower0.7ex\hbox{$2$}}} \) ) of RSP after the RSP dose was longest in the liver (17.6 h) and shortest in the spleen (1.2 h). The \(\)\(t_{{\raise0.7ex\hbox{$1$} \!\mathord{\left/ {\vphantom {1 2}}\right.\kern-\nulldelimiterspace} \!\lower0.7ex\hbox{$2$}}} \) of 9-OHRSP after the RSP dose was shorter in plasma (3.4 h) and other tissues (~8–11 h) than that for RSP but it was longer in the spleen. However, the \(\)\(t_{{\raise0.7ex\hbox{$1$} \!\mathord{\left/ {\vphantom {1 2}}\right.\kern-\nulldelimiterspace} \!\lower0.7ex\hbox{$2$}}} \) of 9-OHRSP after the 9-OHRSP dose was shorter in most tissues as compared to the \(\)\(t_{{\raise0.7ex\hbox{$1$} \!\mathord{\left/ {\vphantom {1 2}}\right.\kern-\nulldelimiterspace} \!\lower0.7ex\hbox{$2$}}} \) of 9-OHRSP after the RSP dose. The area under the concentration-time curve (AUC) of RSP and 9-OHRSP was 6–67 times higher in the plasma and tissues than in the brain. AUCs of 9-OHRSP in tissues after the RSP dose were 2–5 times higher than those for RSP, except in the brain, where AUCs of RSP and 9-OHRSP were similar. Conclusion: Pharmacokinetics of 9-OHRSP in many tissues were different after RSP and 9-OHRSP doses. The reason for disproportionate brain levels of 9-OHRSP is not clear. The overall exposure to active drug in the brain as represented by AUC was similar after the RSP and 9-OHRSP doses and the 9-OHRSP is probably an equal contributor to the pharmacological actions of RSP.
Investigation of Wüstite (FeO) Dissolution: Implications for Reductive Dissolution of Ferric Oxides

The pH-dependent dissolution flux of FeO (wustite, a ferrous oxide) was measured in this study; flux = k{H+}n (mol/m2/s), where k = 10−4.95 and n = 0.64. This flux was consistent with theoretical p...
Spatial Epidemiology of Recently Acquired HIV Infections across Rural and Urban Areas of North Carolina

Transmission of HIV continues in the United States (US), despite prevention efforts aimed at education and treatment. Concurrently, drug resistance in HIV, particularly in patients being infected with HIV for the first time, poses a threat to the continued success of treatment for HIV positive individuals. In North Carolina, nearly one in five individuals with acute HIV infection (AHI) is infected with a drug-resistant strain, a phenomenon known as transmitted drug resistance (TDR). Few studies of AHI or TDR take into account both the spatial aspects of residence at time of infection and the genetic characteristics of the viruses, and questions remain about how viruses are transmitted across space and the rural-urban divide. Using AHI strains from North Carolina, we examined whether differences exist in the spatial patterns of AHI versus AHI with TDR, as well as whether the genetic characteristics of these HIV infections vary by rural-urban status and across Health Service Areas. The highest amounts of TDR were detected in persons under age 30, African Americans, and men who have sex with men (MSM) - similar to the populations where the highest numbers of AHI without TDR are observed. Nearly a quarter of patients reside in rural areas, and there are no significant differences between rural and urban residence among individuals infected with drug resistant or drug susceptible viruses. We observe similar levels of genetic distance between HIV found in rural and urban areas, indicating that viruses are shared across the rural-urban divide. Genetic differences are observed, however, across Health Service Areas, suggesting that local areas are sites of genetic differentiation in viruses being transmitted to newly infected individuals. These results indicate that future efforts to prevent HIV transmission need to be spatially targeted, focusing on local-level transmission in risky populations, in addition to statewide anti- HIV efforts.
A Hybrid Method for UXO vs. Non-UXO Discrimination

Remediation of sites contaminated by unexploded ordnance is complicated by the problem of discriminating between buried conductors that are intact munitions and those that are harmless scrap metal. Here we present two distinct approaches of object discrimination, both of which rely on training data in the form of polarizability curves. These curves show remarkable similarity for same-type objects over a broad range of depths and attitudes, but marked differences when comparing curves from different object types. The first method, called the “voting scheme,” compares field data polarizabilities against templates in a series of cross validations. The second method applies Bayesian statistics on features extracted from the polarizabilities. Here the methods are applied to a 346 element dataset. The voting scheme misclassified fewer UXO objects, but at a cost of more false digs. A hybrid technique combining both methods generates an ordered dig list that ensures efficient use of cleanup resources. For the dat...
Degenerate amplification with semiconductor diodes due to a self-generated avalanche-resonance pump

The features of parametric degenerate and quasidegenerate amplification in silicon avalanche diodes are described for conditions of an optimised self-generated pumping component in the region of the characteristic avalanche-resonance frequency. The signal-frequency gain was observed to be strongly dependent on the pump-voltage amplitude.
Discovering information behavior in sense making. III: the person

This article, the third of three, used the methods of an ethnography of communication to explore the individual information behavior in sense making of participants in the annual work planning of a unit of a public agency. In particular, this article focuses on how people capture and process meaning from their situation. The analysis identified personal sense making styles that included cognitive, affective, and conative (action instinct) elements. These styles seem to also reflect a person's role in the organization and the work planning task. Given that participants in the work planning process had their own personal sense making styles and that these styles tended to vary across participants, it is not surprising that there were clashes in style. This fact was both a strength and a weakness in the sense making that was required for work planning, a complex information intensive task. Diversity of approach, perspective, opinion, and interpretation led to the crafting of strategies that served the purposes of the organization in a richer way than did any individual strategy. Diversity of approach also led to frustration over the amount of time that it took to tie together the different senses and points of view into agreement on actions, only to have these agreements unravel as new cues from the environment suggested the need for modification to at least some participants. Understanding the nature and diversity of sense making styles among members of work teams may aid the team in taking advantage of the range of sense-making skills that are present and lessen the conflicts that arise when different sense-making skills clash. The three parts of the study dealing with time and timing, the social, and the personal are brought together in a brief conceptual synthesis at the end. © 1997 John Wiley & Sons, Inc.
An elderly woman with asthma, eosinophilia, and septic shock.

Her asthma is poorly controlled despite prednisone therapy, and her eosinophil count is high. What is the likely cause?
Stress rapidly increases alpha 1d adrenergic receptor mRNA in the rat dentate gyrus

Abstract The hippocampal formation is a highly plastic brain region that is sensitive to stress. It receives extensive noradrenergic projections, and noradrenaline is released in the hippocampus in response to stressor exposure. The hippocampus expresses particularly high levels of the α1D adrenergic receptor (ADR) and we have previously demonstrated that α1d ADR mRNA expression in the rat hippocampus is modulated by corticosterone. One of the defining features of a stress response is activation of the hypothalamic pituitary adrenal (HPA) axis, resulting in the release of corticosterone from the adrenal glands. However, the effect of stress on hippocampal expression of α1d ADR mRNA has not been determined. In this study, male rats were exposed to inescapable tail shock, loud noise or restraint, and the effect on α1d ADR mRNA expression in the hippocampus was determined by semi-quantitative in situ hybridization. All three stressors resulted in a rapid upregulation of α1d ADR mRNA in the dentate gyrus, with expression peaking at approximately 90 min after the start of the stressor. Physical activity has previously been reported to counteract some of the effects of stress that occur within the dentate gyrus. However, 6 weeks of voluntary wheel running in rats did not prevent the restraint stress-induced increase in α1d ADR mRNA expression in the dentate gyrus. Although the function of the α1D ADR in the dentate gyrus is not known, these data provide further evidence for a close interaction between stress and the noradrenergic system in the hippocampus.
Adhesion of polymeric films to pharmaceutical solids

The two major forces influencing polymer adhesion include the strength of the interfacial bonds between the polymeric film and the surface of the solid and the internal stresses within the film coating. While good adhesion between the polymer and the substrate is desirable for pharmaceutical products, the small size of the dosage form and the non-uniform surface roughness have created difficulties in assessing polymer adhesion. In this review, the experimental devices and procedures used to quantitate polymer adhesion are addressed. The affects of the physical and chemical properties of the substrate, including surface roughness and tablet hydrophobicity, on adhesion of a polymer to either tablets or capsules are discussed. The influence of the plasticizers, pigments, and solvents in film coating formulations on polymer adhesion, and the effects of aging of the coated solids on adhesion of polymers to tablets and capsules are also discussed.
Comparative ultrastructure of the cellular components of the unconstricted notochord in the sturgeon and the lungfish.

Unconstricted notochords are found in only a few extant vertebrates. Within the bony fishes the notochord is present throughout life in the sturgeons and the lungfishes. To better understand the function of this organ, the cellular ultrastructure of the notochord was examined in the shortnose sturgeon, Acipenser brevirostratus, and in the African lungfish, Protopterus annectens. In both species, the medulla of the notochord consists of vacuolated cells connected by desmosomes. The vacuoles are surrounded by a dense cytoplasmic network of intermediate filaments. In Acipenser, the cuboidal to columnar basal cells are avacuolate and contain an extensive network of rough endoplasmic reticulum. In Protopterus, the cytoplasm of the basal cells lacks rough endoplasmic reticulum and often contains a large central vacuole surrounded by a network of intermediate filaments. Cells resembling fibroblasts are found in the fibrous sheath of the notochord of the lungfish, but the fibrous sheath of the sturgeon is acellular. On the basis of the structures observed in the two species, the medulla of the notochord has many of the characteristics of a keratinized epithelium, and the fibrous sheath may be derived from different cellular sources. J. Morphol. 236:75-104, 1998. © 1998 Wiley-Liss, Inc.
Transbronchoscopic Lung Biopsy for Diffuse Pulmonary Diseases: Technique and Results in 450 Cases

We have described a technique of transbronchoscopic biopsy of the lung and the use of this technique in patients with diffuse diseases of the lungs. Satisfactory pulmonary tissue was obtained in 378 of 450 cases (84 percent). Pneumothorax was noted in 14 percent of the patients, and mediastinal emphysema and significant bleeding each were encountered in about 1 percent. There was one death. We have found that transbronchoscopic lung biopsy has been helpful in the diagnosis of diffuse pulmonary disease.
The Pilgrimage of Joel Andrews: Aging in the Autobiography of a Yankee Farmer

Autobiographical writing offers a vast and virtually untapped resource for the historical phenomenology of aging. This essay interprets the autobiography of Joel Andrews—an aging Yankee farmer whose life spanned the period from the American Revolution to the end of the Civil War. We attempt to recreate the poignance and integrity of this ordinary man's struggle with aging and death within the context of his own historical circumstances and religious beliefs. In particular, the essay argues that Andrews' autobiography both reflects and helps accomplish his central task in old age: the religiously sanctioned transition from physical to spiritual man. Andrews' experience provides an interesting contrast to contemporary ideas about health and vitality in old age.
Test-retest reliability in a computer-based medical history.

The authors developed a computer-based medical history for patients to take in their homes via the internet. The history consists of 232 ‘primary’ questions asked of all patients, together with more than 6000 questions, explanations, and suggestions that are available for presentation as determined by a patient's responses. The purpose of this research was to measure the test–retest reliability of the 215 primary questions that have preformatted, mutually exclusive responses of ‘Yes,’ ‘No,’ ‘Uncertain (Don't know, Maybe),’ ‘Don't understand,’ and ‘I'd rather not answer.’ From randomly selected patients of doctors affiliated with Beth Israel Deaconess Medical Center in Boston, 48 patients took the history twice with intervals between sessions ranging from 1 to 35 days (mean 7 days; median 5 days). High levels of test–retest reliability were found for most of the questions, but as a result of this study the authors revised five questions. They recommend that structured medical history questions that will be asked of many patients be measured for test–retest reliability before they are put into widespread clinical practice.
A 122.5-kilobase deletion of the P gene underlies the high prevalence of oculocutaneous albinism type 2 in the Navajo population.

Oculocutaneous albinism (OCA) is a genetically heterogeneous disorder. There are four known types of OCA: OCA1–OCA4. The clinical manifestations of all types of OCA include skin and hair hypopigmentation and visual impairment. Although there are a few documented observations of high frequency of albinism among Native Americans, including the Hopi, Zuni, Kuna, Jemez, Laguna, San Juan, and Navajo, no causative molecular defect has been previously reported. In the present study, we show that albinism in one Native American population, the Navajo, is caused by a LINE-mediated 122.5-kilobase deletion of the P gene, thus demonstrating that albinism in this population is OCA2. This deletion appears to be Navajo specific, because this allele was not detected in 34 other individuals with albinism who listed other Native American origins, nor has it been reported in any other ethnic group. The molecular characterization of this deletion allele allowed us to design a three-primer polymerase chain reaction system to estimate the carrier frequency in the Navajo population by screening 134 unrelated normally pigmented Navajos. The carrier frequency was found to be ∼4.5%. The estimated prevalence of OCA2 in Navajos is between ∼1 per 1,500 and 1 per 2,000. We further estimate that this mutation originated 400–1,000 years ago from a single founder.
Effects of varying the electrical conductivity of the medium between the heart and the body surface on the epicardial and praecordial electrocardiogram in the pig

The effects of varying the electrical conductivity of the medium between the heart and the body surface on the epicardial and praecordial electrocardiograms during porcine myocardial ischaemia were studied. Simple application of saline-soaked gauze pads to the anterior epicardial surface with the chest open caused a marked reduction in the amplitude of the epicardial electrocardiogram. An even greater reduction occurred when the chest was closed with three saline-soaked pads placed in the praecordial space. A drastic reduction in the amplitude of epicardial electrocardiograms was also observed as the praecordial space was filled with Tyrode's solution. Air trapping in the precordial space abolished S-T elevation from the praecordial tracing. When the chest was closed over only one moist gauze pad, a cyclic and reciprocal fluctuation in the amplitudes of simultaneous epicardial and praecordial electrograms was observed. Anterior wall ischaemia could be made to simulate inferior, high lateral or subendocardial ischaemia by merely changing the position of a moistened gauze bridge while the chest was open. Furthermore, inadvertent contact between the anterior cardiac surface and surrounding tissues during anterior wall ischaemia in an open-chest pig caused a marked reduction in the amplitude of the epicardial electrocardiogram. Thus it is shown that the conductivity of the media surrounding the heart can profoundly influence the amplitude and configuration of the epicardial and body surface electrocardiograms. Inadvertent contact between the heart and surrounding tissues by surgical instruments, sponges, pools of blood or saline might distort the results. Likewise, clinical conditions which alter conductivity between the heart and chest wall could influence the body surface electrocardiogram.
Protection against Plasmodium chabaudi malaria induced by immunization with apical membrane antigen 1 and merozoite surface protein 1 in the absence of gamma interferon or interleukin-4.

Strategies to optimize formulations of multisubunit malaria vaccines require a basic knowledge of underlying protective immune mechanisms induced by each vaccine component. In the present study, we evaluated the contribution of antibody-mediated and cell-mediated immune mechanisms to the protection induced by immunization with two blood-stage malaria vaccine candidate antigens, apical membrane antigen 1 (AMA-1) and merozoite surface protein 1 (MSP-1). Immunologically intact or selected immunologic knockout mice were immunized with purified recombinant Plasmodium chabaudi AMA-1 (PcAMA-1) and/or the 42-kDa C-terminal processing fragment of P. chabaudi MSP-1 (MSP-142). The efficacy of immunization in each animal model was measured as protection against blood-stage P. chabaudi malaria. Immunization of B-cell-deficient JH−/− mice indicated that PcAMA-1 vaccine-induced immunity is largely antibody dependent. In contrast, JH−/− mice immunized with PcMSP-142 were partially protected against P. chabaudi malaria, indicating a role for protective antibody-dependent and antibody-independent mechanisms of immunity. The involvement of γδ T cells in vaccine-induced PcAMA-1 and/or PcMSP-142 protection was minor. Analysis of the isotypic profile of antigen-specific antibodies induced by immunization of immunologically intact mice revealed a dominant IgG1 response. However, neither interleukin-4 and the production of IgG1 antibodies nor gamma interferon and the production of IgG2a/c antibodies were essential for PcAMA-1 and/or PcMSP-142 vaccine-induced protection. Therefore, for protective antibody-mediated immunity, vaccine adjuvants and delivery systems for AMA-1- and MSP-1-based vaccines can be selected for their ability to maximize responses irrespective of IgG isotype or any Th1 versus Th2 bias in the CD4+-T-cell response.
Stability and eigenvalue bounds of the flow of a dipolar fluid between two parallel plates

In this article, we derive the Orr–Sommerfeld equation for the stability of parallel flows of a dipolar fluid. The classical results found by Squire, for viscous Newtonian fluids, are generalized to the case of dipolar fluids. A sufficient condition for stability is obtained for dipolar fluids and eigenvalue bounds for the Orr–Sommerfeld equation are found.
Detecting single stranded DNA with a solid state nanopore

Voltage biased solid-state nanopores are used to detect and characterize individual single stranded DNA molecules of fixed micrometer length by operating a nanopore detector at pH values greater than ∼11.6. The distribution of observed molecular event durations and blockade currents shows that a significant fraction of the events obey a rule of constant event charge deficit (ecd) indicating that they correspond to molecules translocating through the nanopore in a distribution of folded and unfolded configurations. A surprisingly large component is unfolded. The result is an important milestone in developing solid-state nanopores for single molecule sequencing applications.
BOND RATING CHANGES AND URBAN FISCAL STRESS: LINKAGE AND PREDICTION

The empirical investigation of urban fiscal stress could be characterized as a wealth of independent variables in search of an appropriate dependent variable. In the array of important social, economic and fiscal measures which influence urban fiscal stress, none alone appears to provide an adequate surrogate for it. Municipal bond ratings have been proffered as an appropriate dependent variable for studies of urban fiscal stress. While far from perfect, ratings have the advantages of both simplicity and their stated purpose of summarizing and reflecting the various socio-economic and fiscal attributes which result in continued fiscal health. This paper first examines the theoretical and practical arguments in support of bond ratings as a surrogate measure of fiscal stress. We find that whether or not ratings are accepted as an adequate measure of fiscal health, they are sufficiently important to warrant further study. We then develop a model to predict bond rating changes using socioeconomic and fiscal data from time periods prior to the rating change. Based on a sample of all cities with populations over 25.000 persons which experienced a rating change between 1975 and 1980, the model is 89% accurate in predicting up and downgraded cities.
Orientation selectivity in the cat's striate cortex is invariant with stimulus contrast

Extracellular responses of single units in striate cortex of the cat were studied quantitatively. Sinusoidal gratings were used as stimuli and the variables of interest were orientation and contrast. Specifically, we wanted to determine if orientation tuning was dependent on contrast. Of 45 cells studied in detail, two basic types of contrast-response pattern were observed, but most patterns were intermediate between these extremes. In one type, responses increased approximately linearly with log contrast while in the second, saturation was found at low contrast levels. For all these cells, orientation tuning characteristics were independent of contrast. An additional observation, made from 14 cells, was that stimuli presented at non-optimal orientations can suppress responses to below the general maintained discharge levels. In eight of these cases, the inhibition was clearly contrast-dependent.
Top Wealth Shares in the United States: 1916-2000: Evidence from Estate Tax Returns

This paper presents new homogeneous series on top wealth shares from 1916 to 2000 in the United States using estate tax return data. Top wealth shares were very high at the beginning of the period but have been hit sharply by the Great Depression, the New Deal, and World War II shocks. Those shocks have had permanent effects. Following a decline in the 1970s, top wealth shares recovered in the early 1980s, but they are still much lower in 2000 than in the early decades of the century. Most of the changes we document are concentrated among the very top wealth holders with much smaller movements for groups below the top 0.1%. Consistent with the Survey of Consumer Finances results, top wealth shares estimated from Estate Tax Returns display no significant increase since 1995. Evidence from the Forbes 400 richest Americans suggests that only the super-rich have experienced significant gains relative to the average over the last decade. Our results are consistent with the decreased importance of capital income at the top of the income distribution documented by Piketty and Saez (2003) and suggest that the rentier class of the early century is not yet reconstituted. The most plausible explanations for the facts are perhaps the development of progressive income and estate taxation which has dramatically impaired the ability of large wealth holders to maintain their fortunes, and the democratization of stock ownership which now spreads stock market gains and losses much more widely than in the past.
MEMS ultrasonic transducers for highly sensitive Doppler velocity sensor for low velocity measurement

This paper describes a novel, highly-sensitive ultrasonic Doppler velocity sensing system for low velocity measurement in portable navigation systems. It is a compact velocity sensing system, in which MEMS ultrasonic transducers are incorporated with phase-locked-loop (PLL) circuitry for frequency detection and signal processing. The achieved voltage-velocity sensitivity is 0.22 V/(mm/s) and the minimum detectable velocity is 0.67 mm/s, corresponding to 0.11 Hz in Doppler frequency. To the best of our knowledge, the minimum detectable velocity is the best reported in literature. Also, the output of the PLL is a DC voltage linearly related to the velocity, and there is no need to convert the frequency shift to analog voltage.
From motility to virulence: sensing and responding to environmental signals in Vibrio cholerae

Sensing its changing environment is key for Vibrio cholerae when making the transition from an aquatic lifestyle to one more suited to a human host. An inverse correlation between motility and virulence gene expression has been reported, with the NADH : ubiquinone oxidoreductase system which powers motility by generating a sodium-motive force, playing a pivotal role. Recent studies have demonstrated that bile inhibits activity of the transcription factor ToxT, a protein responsible for direct activation of numerous virulence gene promoters. In addition, recent technological advances have allowed for the analysis of in-vivo-induced genes and assessment of their timing of expression. Use of recombinase-based in vivo expression technology has revealed that the toxin-coregulated pilus (a colonization factor) is expressed before cholera toxin. Components of an acid-tolerance response system have also been found using this method as well as signature-tagged mutagenesis. Finally, a role for quorum sensing in regulation of virulence gene expression has recently been established.
Low 24-Hour Adiponectin and High Nocturnal Leptin Concentrations in a Case-Control Study of Community-Dwelling Premenopausal Women With Major Depressive Disorder: The Premenopausal, Osteopenia/Osteoporosis, Women, Alendronate, Depression (POWER) Study

Objective Major depressive disorder (MDD) is associated with immune system dysfunction and disruption of multiple circadian systems. Adiponectin is an adipocytokine with anti-inflammatory and antiatherogenic effects. Circulating concentrations are inversely related to adiposity and risks of metabolic syndrome and diabetes mellitus. Our goals were (1) to establish whether premenopausal women with MDD exhibit decreased plasma adiponectin concentrations and/or disruption of circadian adiponectin rhythmicity; (2) to assess whether there is a relationship between adiponectin and MDD; and (3) to explore the temporal relationships among adiponectin, leptin, corticotropin, and cortisol secretion. Method We conducted a case-control study of community-dwelling premenopausal women with DSM-IV MDD (n = 23) and age- and body mass index (BMI)-matched control subjects (n = 23). Main outcome measures were circulating concentrations of adiponectin, leptin, corticotropin, and cortisol measured hourly for 24 hours. Subjects were recruited from July 1, 2001, to February 28, 2003. Results Women with MDD had approximately 30% lower mean 24-hour concentration of adiponectin than did control subjects. Adiponectin concentration was inversely related to depression severity and total duration of disease, suggesting a causal link. In contrast, mean nocturnal leptin concentration was higher in the MDD versus control groups. Mean leptin concentration was inversely related to cortisol and adiponectin concentrations, both in subjects with depression and in control subjects. In cross-correlation analyses, the relationship between corticotropin and cortisol concentrations was stronger in women with MDD than in control subjects, a finding consistent with hypothalamic-pituitary-adrenal (HPA) axis activation in MDD. Conclusions In premenopausal women with MDD, reduced daily adiponectin production may increase the risk of diabetes mellitus, and elevated leptin may contribute to osteoporosis.
Targeting the Transforming Growth Factor-β Signaling Pathway in Human Cancer

The transforming growth factor-ss (TGF-beta) signaling pathway plays a pivotal role in diverse cellular processes. TGF-beta switches its role from a tumor suppressor in normal or dysplastic cells to a tumor promoter in advanced cancers. It is widely believed that the Smad-dependent pathway is involved in TGF-beta tumor-suppressive functions, whereas activation of Smad-independent pathways, coupled with the loss of tumor-suppressor functions of TGF-beta, is important for its pro-oncogenic functions. TGF-beta signaling has been considered a useful therapeutic target. The discovery of oncogenic actions of TGF-beta has generated a great deal of enthusiasm for developing TGF-beta signaling inhibitors for the treatment of cancer. The challenge is to identify the group of patients where targeted tumors are not only refractory to TGF-beta-induced tumor suppressor functions but also responsive to the tumor-promoting effects of TGF-beta. TGF-beta pathway inhibitors, including small and large molecules, have now entered clinical trials. Preclinical studies with these inhibitors have shown promise in a variety of different tumor models. Here, we focus on the mechanisms of signaling and specific targets of the TGF-beta pathway that are critical effectors of tumor progression and invasion. This report also examines the therapeutic intervention of TGF-ss signaling in human cancers.
The Development of Sex Differences in Friendship Patterns and Peer Group Structure During Adolescence

In a naturalistic study of sex differences in friendship patterns and peer group structure during adolescence, 130 groups composed of 321 adolescents were observed in three high schools and six out-of-school settings. No sex differences were found in the percentages of males and females observed in dyads or with a companion of the opposite-sex. Male friends knew each other longer than did female friends or male-female friends. Lastly, during adolescence, groups observed out of school became smaller and more heterosexual, while in-school groups remained large and unisexual. The need for further observational research on the patterning of male and female relationships during the transition from childhood to early adolescence was emphasized.
A statistical method for studying correlated rare events and their risk factors

Longitudinal studies of rare events such as cervical high-grade lesions or colorectal polyps that can recur often involve correlated binary data. Risk factor for these events cannot be reliably examined using conventional statistical methods. For example, logistic regression models that incorporate generalized estimating equations often fail to converge or provide inaccurate results when analyzing data of this type. Although exact methods have been reported, they are complex and computationally difficult. The current paper proposes a mathematically straightforward and easy-to-use two-step approach involving (i) an additive model to measure associations between a rare or uncommon correlated binary event and potential risk factors and (ii) a permutation test to estimate the statistical significance of these associations. Simulation studies showed that the proposed method reliably tests and accurately estimates the associations of exposure with correlated binary rare events. This method was then applied to a...
Composite operational amplifiers: Generation and finite-gain applications

A practical and effective general approach is presented for extending the useful operating frequencies and improving the performance of linear active networks realized using operational amplifiers (OA's). This is achieved by replacing each OA in the active network by a composite operational amplifier (CNOA) constructed using N OA's. The technique of generating the CNOA's for any given N is proposed. The realizations employing the CNOA are examined according to a stringent performance criterion satisfying such important properties as extended bandwidth, stability with one- and two-pole OA models, low sensitivity to the components and OA mismatch, and wide dynamic range. Several families of CNOA's, for N = 2, 3, and 4 , are shown to satisfy ,the suggested performance criterion. In this contribution, the CNOA's applications in inverting, noninverting, and differential finite-gain amplifiers are given and shown theoretically and experimentally to compare favorably with the state-of-the-art realizations using the same number of OA's. Applications of the CNOA in inverting integrator and active filter realizations are presented in a companion contribution [32].
INTRODUCTION TO MEDICAL PHYSIOLOGY: CELLULAR MEMBRANES AND TRANSMEMBRANE TRANSPORT OF SOLUTES AND WATER

This article summarizes the comments made in the introductory session of the Medical Physiology course taught at the University of Alabama School of Medicine. The main thesis is that learning physiology is easier when fundamental principles are first delineated. Four general principles of physiology (mass balance, force-flow, capacitance, and equilibrium) are discussed. Clinical medicine becomes more comprehensible when these basic principles are understood. Cellular Physiology is taught first because it forms the conceptual basis for what follows in the course. The idea that the root of clinical medicine lies in the basic sciences is emphasized.
Fixed low-dose drug combination for the treatment of hypertension

The goal of treating hypertension is to maximize therapeutic efficacy without untoward side effects. The accepted approach is to start treatment with a low dose of a single drug and then titrate it upward as needed to achieve a better therapeutic effect. However, higher doses of administered individual drugs increase the frequency and severity of side effects. A rational combination of individual drugs administered in low doses is preferable because it is associated with a high degree of efficacy, low incidence or severity of side effects, and high patient compliance. The most commonly used drug combinations are as follows: (1) diuretics with potassium-sparing agents; (2) beta-adrenergic blockers with diuretics; (3) angiotensin-converting enzyme inhibitors with diuretics; (4) angiotensin II receptor blockers with diuretics; and (5) angiotensin-converting enzyme inhibitors with calcium-channel blockers.
A note on the relationship between correlation and circular error probability (CEP)

This note investigates the effects of ignoring correlation (p) as is sometimes done when estimating or placing confidence intervals on circular error probability (CEP). It is shown that better estimates of CEP can be made if the axis is rotated [5] so that the estimate of p is zero. It is also shown that ignoring variability in estimating correlation can affect the confidence intervals on CEP or the placing of a lower bound on the probability content of a circle.
Management of hypertension in the hemodialysis population: a review of the literature.

Objective : The objective of this paper was to propose an algorithm for approaching hypertensive hemodialysis patients admitted to the hospital for hypertensive urgency. Methods : A literature search was conducted using PubMed (Medline). Articles selected were limited to humans and the English language. Results : We identified eight management modalities including: short-daily and nocturnal dialysis, sodium restriction, sodium profiling, antihypertensive medications, sympathetic denervation, bilateral nephrectomy, and bioimpedance spectroscopy. The benefits and drawbacks of each were investigated and discussed before implementation into the algorithm. Discussion : The algorithm presented suggests a linear approach to patient care, but treatment modalities may not be mutually exclusive, and additional factors, such as patient compliance and individual health status, should be taken into account to provide patients with optimum care. Keywords : hypertension; hemodialysis; algorithm; sodium dialysate; anti-hypertensive medication (Published: 31 July 2014) Citation : Journal of Community Hospital Internal Medicine Perspectives 2014, 4 : 24055 - http://dx.doi.org/10.3402/jchimp.v4.24055
CHANGES IN EGG SIZE AND CLUTCH SIZE WITH ELEVATION IN A WYOMING POPULATION OF MOUNTAIN BLUEBIRDS

Abstract Few studies have examined how avian life-history traits vary within populations as elevation increases and climate becomes more severe. We compared egg and clutch sizes of Mountain Bluebirds (Sialia currucoides) nesting at two elevations (1500 m and 2500 m above sea level) in the Bighorn Mountains of Wyoming over two years. Eggs laid by females at the high-elevation site were, on average, significantly (6%) smaller in volume than eggs laid by their lower-elevation counterparts. Across elevations, egg size showed a significant positive correlation with female body condition (weight relative to size), and high-elevation females had significantly lower indices of condition than low-elevation females. Temperatures during clutch formation were colder at the high-elevation site, and egg size was negatively related to temperature after controlling for the effects of female condition. Clutches of females at high elevations were, on average, marginally smaller (by 5%, 0.3 eggs) than clutches of low-elevat...
Effects of implanted radio transmitters with percutaneous antennas on the behavior of Canada Geese

Abstract We examined whether surgically-implanted radio transmitters with percutaneous antennas affected behavior of Lesser Canada Geese (Branta canadensis parvipes) in Anchorage, Alaska. We implanted either a 26-g VHF radio transmitter or a larger VHF radio that was the same mass (35 g) and shape as a satellite transmitter in the coelom of adult females captured during molt in 2000. A control group of females was marked with leg bands. We simultaneously observed behavior of radio-marked and control females from 4–62 d following capture. We observed no differences in the proportion of time birds in different treatments allocated among grazing, resting, comfort, walking, and alert behavior. Females in different treatments spent a similar proportion of time in the water. Implantation of radio transmitters did not affect the frequency of agonistic interactions. We conclude that coelomic radio transmitters with percutaneous antennas had minimal effects on the behavior of Canada Geese.
Las intrucciones a los superintendentes de villas como fuentes para la historia urbana

Las Instrucciones a los Superintendentes de villas o Comisionados se hallan en los archivos nacionales y en el Archivo General de Indias, de Sevilla, generalmente contenidas en los autos de fundacion de cada una de las poblaciones erigidas en Chile durante el siglo XVIII. A diferencia de las Actas de Fundacion de ciudades indianas, que han merecido la atencion de los historiadores, las instrucciones para fundar y poblar en el siglo XVIII chileno no han sido trabajadas en su conjunto, ni se han publicado, aunque el texto integro de tal o cual instruccion, o un extracto de ellas, suele verse incluido en diversas obras de historia urbana.
Orthogonal Evolution of Teams: A Class of Algorithms for Evolving Teams with Inversely Correlated Errors

Several general evolutionary approaches have proven quite successful at evolving teams (or ensembles) consisting of cooperating team members. However, in this paper we demonstrate that the existing approaches have subtle, but significant, weaknesses. We then present a novel class of evolutionary algorithms (orthogonal evolution of teams (OET)) for evolving teams that overcomes these weaknesses. Specifically it is shown that a typical algorithm from the OET class of algorithms successfully generates team members that have fitnesses comparable to those evolved independently and that have inversely correlated errors, which maximizes the teams’ overall performance. Finally it is shown that the OET approach performs significantly better than the standard evolutionary approaches.
General Characteristics of Speculum Mentis

Speculum Mentis was sent to the publisher in August, 1923. With it, Collingwood reached the culmination of his early philosophy of culture. It is a work remarkable for fluency and vividness, as well as scope and boldness. Whatever its merits, Collingwood’s attitude toward it altered as the years went by. He remarks in An Autobiography that at the time he was disappointed at how reviewers were misinterpreting his meaning. He adds in a footnote, written in 1938, the following characteristic piece of self-portraiture: Since writing that sentence [“Speculum Mentis … is a bad book in many ways”] I have read Speculum Mentis for the first time since it was published, and find it much better than I remembered. It is a record, not so very obscure in expression, of a good deal of genuine thinking. If much of it now fails to satisfy me, that is because I have gone on thinking since I wrote it, and therefore much of it needs to be supplemented and qualified. There is not a great deal that needs to be retracted.1
Studying Canada or Paradigms Lost and Found: The Waves of Canadian Historiography

This article is entitled “Studying Canada or Paradigms Lost, Paradigms Found: The Waves of Canadian Historiography” because its purpose is to review the recent record of Canadian historiography and assess its current condition. There has been a sequence of scholarly paradigms in the study of Canadian political culture dating back to the 1920’s and so the article proceeds on the basis of a tripartite periodic division between the earlier Whig-Monumentalist-Essentialist-Idealist phase, the “revisionist” period of the Hartz-Horowitz/Tory Touch approach, and the more recent Postmodern-Pluralist-Contextualist-Eventist tendencies. These approaches are reviewed beginning with the Hartz-Horowitz/Tory-touch thesis as the most dominant paradigm over recent decades. The article then turns to the more recent trends away from this argument by those under certain postmodern influences. It then goes on to ask whether the eschewal of the Whig-Monumentalist-Essentialist-Idealist approach has not been too hasty and in need of review. The article concludes that a broad academic consensus in the field of “Canadian Studies” is not reasonably to be expected in the near future. Scholarly and philosophical names that will come up in the course of the discussion include Ajzenstat, McKay, Vaughan, Horowitz , Forbes, McRae, Granatstein, Romney, Bannister, McNairn, Fierlbeck, McKillop, Careless, Underhill, Morton, Creighton, Innis, Leacock, Grant, Cook, Preece, Binnie, Christian, Gramsci, Foucault, Locke, Tocqueville, Mill, Carlyle, Nietzsche, James, Spencer and others.
Seeds of Destruction

This chapter provides the reader with an understanding and appreciation for the scope and importance of biological threats and the opportunity to see where they may be and have become the desire of terrorist groups and the makings of weapons of mass destruction. The history of biological warfare is covered in depth. These major events are important in helping us understand the issues related to using biological substances against an adversary. The difference between biosecurity and biodefense are explained and then related to homeland security and homeland defense, respectively. This chapter also details how expensive these programs are, with nearly $80 billion having been spent on civilian biodefense since fiscal year 2001 in the United States alone. As discussed herein, there is a significant difference in the reality and the potential of bioterrorism. Bioterrorism on a large scale is a low-probability event. Bioterrorism on a small scale is a fairly routine occurrence with little potential. Biological threats remain very much in the news. Recent examples, such as laboratory incidents, the Ebola outbreak of 2014, and other emerging threats, are covered in this chapter.
Dream of the Mother Language: Myth and History in She Tries Her Tongue, Her Silence Softly Breaks

Originally from Trinidad and Tobago and now a Canadian citizen, Marlene Nourbese Philip writes important poetry that knows its own importance. Not satisfied with speaking from the confines of personal experience and memory, Philip is interested in the larger picture: the relationship of citizens of the African diaspora to their past and future through what Toni Morrison has called "rememory," an active revisioning of history and mythology to parallel and counter the myths of Black inferiority. Neither didactic, like much "political poetry," nor focused on the self, Philip's work is moving in its authenticity of voice and its desire to speak to a large audience. She is concerned with the blocked communication of a people who, like the mythological Philomela, have been kidnapped, enslaved and robbed of their tongue, who must re-member themselves in order to conquer their victimization. In her book, She Tries Her Tongue, Her Silence Softly Breaks, Philip explores the particularities of the Afro-Caribbean experience while making connections between patriarchy and oppression of women around the world. Against a dominant mythology which is ready to privilege the voice of easy communication and blame the suffering for their silence, Philip posits a discourse of dissent through the use of history, mythical imagination and interrogation of the dominant and racist discourses which keep the silent looking backward. Philip's goal is to force an active reconstruction and questioning of the past, particularly of how the imperialist project succeeded in dominating African slaves through "the logic of language." Hybrid in form-a border text which is neither essay nor poemShe Tries Her Tongue juxtaposes texts from many sources, not always telling the reader the origin of a quotation, sometimes mimicking the discourse of the oppressor in fictitious quotations from fictitious books to jar the reader into recognizing the bitter ironies of the colo