cssi/SciSciGPT-SciSciNet huggingface dataset:
Constitutional 560.49 kb chromosome 2p24.3 duplication including the MYCN gene identified by SNP chromosome microarray analysis in a child with multiple congenital anomalies and bilateral Wilms tumor.

Fewer than 100 patients with partial chromosome 2p trisomy have been reported. Clinical features are variable and depend on the size of the duplicated segment, but generally include psychomotor delay, facial anomalies, congenital heart defect, and other abnormalities. We report a 560.49 kb duplication of chromosome 2p in a 13 month-old male with hydrocephaly, ventricular septal defect, partial agenesis of the corpus callosum, and bilateral Wilms tumor. After discovery of bilateral renal masses at four months of age, the child underwent neoadjuvant chemotherapy followed by right radical nephrectomy that revealed triphasic Wilms' tumor. A needle core biopsy on one of two lesions on the left kidney also revealed Wilms tumor. A partial left nephrectomy revealed focally positive margins that necessitated left flank radiotherapy. The tumor karyotype was 46,XY,t(7;8)(q36;p11)[8]/46,XY [12] while his constitutional karyotype was 46,XY, suggesting that the t(7;8)(q36;p11) was associated with the malignancy. Single nucleotide polymorphism (SNP) chromosome microarray analysis of peripheral blood identified a maternally-inherited 560.49 kb chromosome 2p24.3 duplication that involved four OMIM genes: NBAS, DDX1, MYCNOS, and MYCN. SNP array analysis of the tumor revealed the same 2p24.3 duplication. At present, the now 5-year-old boy continues to do well without clinical or radiographic evidence of recurrent disease. This case is instructive because the child's health insurer initially denied authorization for chromosome microarray analysis (CMA), and it took more than one year before such authorization was finally granted. That initial decision to deny coverage could have had untoward health implications for this child, as the identification of constitutional MYCN duplication necessitated surveillance imaging for a number of pediatric malignancies associated with MYCN overexpression/dysregulation.
Abstraction using analysis of subgames

Normal form games are one of the most familiar representations for modeling interactions among multiple agent. However, modeling many realistic interactions between agents results in games that are extremely large. In these cases computing standard solutions like Nash equilibrium may be intractable. To overcome this issue the idea of abstraction has been investigated, most prominently in research on computer Poker. Solving a game using abstraction requires using some method to simplify the game before it is analyzed. We study a new variation for solving normal form games using abstraction that is based on finding and solving suitable sub games. We compare this method with several variations of a common type of abstraction based on clustering similar strategies.
The Management of Bipolar Disorder During and After Pregnancy

This chapter will discuss the issues of psychiatric management of bipolar disorder (BD) both during and after pregnancy. The risks and benefits of medication use during pregnancy will be discussed along with the risks of discontinuation of medications for pregnancy. Pharmacological treatments will be discussed in detail. The postpartum time period and its risks for depression, mania, and psychosis will be described, and recommendations for management during this critical time period will be detailed. Medication use during breastfeeding will also be discussed.
Variation in characteristics among gizzard shad populations: The role of impoundment size and productivity

Population characteristics of gizzard shad, Dorosoma cepedianum (Lesueur), an ecologically important fish species in Midwestern and southern USA impoundments, vary widely among water bodies. Impoundment productivity is known to influence population variables (e.g., recruitment, growth, mortality, size and age composition), but the role of impoundment morphometry (e.g., surface area, depth) is unknown. Differences in population characteristics of gizzard shad were compared between large and small impoundments across an impoundment–productivity gradient (indexed by total phosphorus [TP] concentration). Populations shifted from those comprised mostly of low abundances (indexed by catch per unit effort [CPUE], fish/hr of electric fishing) of long-lived, large adults to those comprised of high abundances of short-lived, small adults as TP increased. However, the trends in population variables across the TP gradient were less apparent in small impoundments than in large impoundments owing to considerable variation at a given TP level. Further analysis revealed that CPUE of gizzard shad was lowest in the smallest impoundments (<33 ha surface area) regardless of TP concentrations, probably because of more frequent winter kills. Overall, population characteristics were influenced by both density-dependent effects and impoundment characteristics. Characteristics of gizzard shad were highly variable among populations, which have important consequences for ecosystem structure and function.
Fluorescent proteins detect host structural rearrangements via electrostatic mechanism

The rational design of genetically encoded fluorescent biosensors, which can detect rearrangements of target proteins via interdomain allostery, is hindered by the absence of mechanistic understanding of the underlying photophysics. Here, we focus on the modulation of fluorescence by mechanical perturbation in a popular biological probe: enhanced Green Fluorescent Protein (eGFP). Using a combination of molecular dynamics (MD) simulations and quantum chemistry, and a set of physically motivated assumptions, we construct a map of fluorescence quantum yield as a function of a 2D electric field imposed by the protein environment on the fluorophore. This map is transferable between Tsien’s Class 2 GFP’s, and it allows one to estimate the shifts in fluorescence intensity due to mechanical perturbations directly from MD simulations. We use it in combination with steered MD simulations to put forward a hypothesis for the mechanism of a genetically encoded voltage probe (ArcLight) whose mechanism is currently unde...
Phase-locked, high power, mid-infrared quantum cascade laser arrays

We demonstrate phase-locked, high power quantum cascade laser arrays, which are combined using a monolithic, tree array multimode interferometer, with emission wavelengths around 4.8 μm. A maximum output power of 15 W was achieved from an eight-element laser array, which has only a slightly higher threshold current density and a similar slope efficiency compared to a Fabry-Perot laser of the same length. Calculated multimode interferometer splitting loss is on the order of 0.27 dB for the in-phase supermode. In-phase supermode operation with nearly ideal behavior is demonstrated over the working current range of the array.
Étude comparative de coûts entre les poches de gemcitabine prêtes à l’emploi et une fabrication en unité de reconstitution

Resume Introduction Le dose-banding permet de rationaliser la preparation des cytotoxiques. Une nouvelle etape a recemment ete franchie avec la commercialisation de la gemcitabine en poche pour perfusion prete a l’emploi. Quel est l’impact pharmaco-economique de l’utilisation de poches pretes a l’emploi versus une fabrication en unite de preparation ? Methodes Une analyse retrospective des doses de gemcitabine preparees sur trois mois a permis de detailler notre consommation, et par modelisation, de definir un intervalle de prescription pour chaque dosage de poche prete a l’emploi. Une etude de couts compares a evalue le cout du medicament, du materiel de fabrication et le temps de preparation. Resultats Pour un ecart de dose de 5 %, 7,5 % et 10 %, respectivement 67 %, 75 % et 76 % des preparations etaient couvertes par les doses standards. La variation de dose retenue a donc ete celle a 7,5 %. Le cout de fabrication annuel des poches de gemcitabine est d’environ 30 000 € pour les flacons de solution, 32 300 € pour les flacons de poudre, versus 67 300 € pour les poches pretes a l’emploi. Un gain d’environ 7,75 minutes de temps preparateur serait realise par preparation. Discussion L’utilisation des poches de gemcitabine pretes a l’emploi permettrait une couverture pertinente des doses realisees. Le surcout annuel pour l’utilisation des poches pretes a l’emploi serait de 37 200 € pour notre etablissement. Il peut se justifier par les benefices attendus : securisation du circuit du medicament, gain de temps preparateur…
Contraception for Women Living with HIV

For women living with HIV, there are several issues to consider in attending to their reproductive health and contraceptive needs. In this chapter we review common medical comorbidities, pregnancy-associated risks, and reproductive health concerns that present among HIV-infected women. Although most contraceptive methods are safe for women with HIV, careful consideration of other comorbidities and current medications are important in helping the individual select an ideal contraceptive option. While controversies exist regarding the potential for certain hormonal contraceptives to contribute to increased HIV transmission and progression, the current research is inconclusive and does not influence current contraceptive recommendations. As several antiretroviral drugs may interact with hormonal contraceptives to reduce effectiveness, careful patient counseling during method selection and encouragement of dual protection with condoms are important.
Stochastic resonance and noise-induced phase coherence

We prove a close relation between stochastic resonance and the phenomenon of noise-induced synchronization. The method proceeds by assigning instantaneous phases to input and output signals and by reformulating the rates of the standard two-state system in terms of the input-output phase difference. We are able to analytically derive criteria for noise-induced frequency and effective phase locking. The implications of both phenomena for stochastic resonance are discussed.
Evaluation of positive patch test reactions using optical coherence tomography: A pilot study.

INTRODUCTION Patch testing is the gold standard for evaluating allergic contact dermatitis (ACD), yet current interpretation methods are limited by their subjectivity and possible variability between observers. Optical coherence tomography (OCT) imaging enables noninvasive in vivo skin visualization and holds promise as an objective method of patch test interpretation. OBJECTIVE To evaluate the micromorphological changes of patch test reactions and identify objective, quantitative OCT markers that correlate with clinically graded patch test reactions. RESULTS A total of 25 patch test reactions (7 grade-0, 4 grade-1+, 14 grade-2+) from 7 patients underwent OCT evaluation. Increased epidermal thickness and density was qualitatively observed in grade 1+ and grade 2+ allergic reactions while well-demarcated, signal-free cavities were observed in all grade 2+ reactions. Attenuation coefficients significantly increased across the three reaction grades (2.58 ± 0.092, 2.96 ± 0.121, 3.05 ± 0.065; P < 0.01). Cutaneous blood flow at 0.35 mm monotonically increased with reaction grade severity and blood measurements significantly differed across the three reaction grades (0.053 ± 0.011 mm/s, 0.078 ± 0.015 mm/s, and 0.121 ± 0.008 mm/s; P < 0.01). CONCLUSIONS AND RELEVANCE Attenuation coefficient and cutaneous blood flow at 0.35 mm correlate with clinically graded patch test reactions and hold promise as objective, quantitative markers. OCT may help dermatologists differentiate clinical scoring of allergic reactions in patch test and thereby improve their diagnostic accuracy and interpretation of patch test reactions.
Dam building by the illiberal modernisers: ideology and changing rationales in Rwanda and Tanzania

Dams have a prominent historical status, imagined through high-modernist ideology as the premier infrastructure project, delivering electricity, irrigation and the spectacle of development. However, the decade from the mid-1990s to the mid-2000s saw few dams constructed and major funders such as the World Bank pull out. Dams have returned over the past decade, particularly in authoritarian countries in Africa. This sparks questions about the contemporary state of politics and development ideology. This article, using case studies from Rwanda and Tanzania, asks whether high-modernist ideology has returned and justifies the dam resurgence. The article finds, however, that high modernism now plays an indirect role. It underpins broader development-focused state building missions that are central to Rwanda and Tanzania and also rationalises pyramidal, expertcentric decision making and depoliticised ideas imbuing electricity itself with development. Dams are therefore built for their hydropower, rather than for their modernising spectacle; moreover, both countries demonstrate sustainable development discourse and critiques of dams’ efficacy. The article concludes that this suggests a more nuanced modernising ideology and somewhat responsive authoritarian states. The article is based on my thesis involving elite-level interviews and ground-level fieldwork with members of each dam’s local community.
L-type voltage-gated Ca2+ channel CaV1.2 regulates chondrogenesis during limb development

All cells, including nonexcitable cells, maintain a discrete transmembrane potential (Vmem), and have the capacity to modulate Vmem and respond to their own and neighbors’ changes in Vmem. Spatiotemporal variations have been described in developing embryonic tissues and in some cases have been implicated in influencing developmental processes. Yet, how such changes in Vmem are converted into intracellular inputs that in turn regulate developmental gene expression and coordinate patterned tissue formation, has remained elusive. Here we document that the Vmem of limb mesenchyme switches from a hyperpolarized to depolarized state during early chondrocyte differentiation. This change in Vmem increases intracellular Ca2+ signaling through Ca2+ influx, via CaV1.2, 1 of L-type voltage-gated Ca2+ channels (VGCCs). We find that CaV1.2 activity is essential for chondrogenesis in the developing limbs. Pharmacological inhibition by an L-type VGCC specific blocker, or limb-specific deletion of CaV1.2, down-regulates expression of genes essential for chondrocyte differentiation, including Sox9, Col2a1, and Agc1, and thus disturbs proper cartilage formation. The Ca2+-dependent transcription factor NFATc1, which is a known major transducer of intracellular Ca2+ signaling, partly rescues Sox9 expression. These data reveal instructive roles of CaV1.2 in limb development, and more generally expand our understanding of how modulation of membrane potential is used as a mechanism of developmental regulation.
Surgery for Spine Disease and Intractable Pain.

Painful conditions, particularly due to head pain, spinal disease, and neuropathic pain, are highly prevalent in modern society, resulting in a significant impact on the individual due to the disability of the condition and the direct cost of associated treatments [...]
Fluorescence up-conversion for differential luminescence thermometry in Ho-doped crystals

Abstract: The use of temperature-sensitive fluorescence up-conversion in Ho doped crystals for non-contact Differential Luminescence Thermometry (DLT) is investigated. The up-conversion fluorescence spectra of Ho3+-doped YLF crystals, subject to pumping within the 5I8 - 5I7 manifold (1899-2066 nm), are measured versus the temperature in a cryostat. Considerable changes in the measured photoluminescence spectra, and in the red, yellow and green upconversion spectra is observed as the temperature is reduced from 300 K to 80 K
7.16 – Thiamin Enzymology

The reactions of thiamin diphosphate, the vitamin B1 coenzyme, on several enzymes are described in this chapter. This coenzyme is an electrophilic covalent catalyst, forming a series of intermediates with its substrates. These intermediates, and their time course of formation and depletion, have recently been characterized. The coenzyme is composed of a thiazolium ring and a 4-aminopyrimidine ring. While the former had been recognized to serve as the electrophilic catalyst by Ronald Breslow, a catalytic role for the 4-aminopyrimidine ring was only recently revealed with the demonstration that it behaves as an acid–base catalyst via its 1′,4′-iminopyrimidine tautomeric form. The support for the involvement of this unusual tautomer in generating the C2-carbanion/ylide from the thiazolium ring is reinforced by the discovery of enzymes that are virtually devoid of amino acid side chains near the coenzyme that could act as acid–base catalysts. A further fascinating feature of thiamin enzymes is the creation of an enzymatic ‘solvent effect’, which helps to stabilize zwitterionic intermediates in the reaction pathway thereby lowering the activation energy of the reactions by as much as 10 kcal mol−1. Thiamin diphosphate is known to participate in both ionic and free radical reactions, adding to its diverse and fascinating chemistry.
Surgical Jeopardy: Play to Learn.

Abstract Background General Surgery residencies use protected education time in various fashions in order to optimize content quality and yield for their learners. This knowledge is tested annually with the American Board for Surgery In-Training Examination (ABSITE) exam and is used to evaluate several aspects of a resident. We hypothesized that using a jeopardy game in educational conference would encourage residents to engage in self-learning and improve ABSITE scores at a single institution. Materials and methods At a single institution, during protected education conference, residents played an hour-long surgical jeopardy game every 7 wk to summarize high yield topics discussed during the previous 6 wk of didactic learning. A 5-point Likert survey was completed by general surgery residents to discern the utility of the game format for learning. The ABSITE category scores were also evaluated from the year before and the year after the game was implemented. Results Twenty-four general surgery residents took the survey with >80% agreeing that the jeopardy format was either a fun or an effective way to learn general surgery topics. Additionally, over 80% of residents thought the game format helped with retention of knowledge. ABSITE categories that had a jeopardy session improved from 65.9% to 70.4% correct (P = 0.0003). ABSITE categories that did not have dedicated jeopardy had a non-significant increase in scores (67.7%-69.9%, P = 0.1). Conclusions Implementing surgical jeopardy as a component of educational conferences in general surgery resident training is correlated with improvement of ABSITE scores. Surgical jeopardy may be easily adopted and implemented to stimulate self-directed learning for residents.
Abstract 2026: Outcomes in elderly patients with non-small-cell lung cancer receiving immune checkpoint inhibitor therapy: A real world experience

Introduction This study examines outcomes in older adults with non-small-cell lung carcinoma (NSCLC) treated with immune checkpoint inhibitors (ICIs) - a population which has been underrepresented in clinical trials. Methods We performed a single-center retrospective study and collected data on safety and toxicity on patients with Stage IV NSCLC aged 65 or greater who were treated with ICI therapy from 2015 through 2017. Efficacy data included overall survival (OS) and progression free survival (PFS). Toxicity data included immune-related adverse events (irAEs) and need for glucocorticoids. Results A total of 48 patients aged 65 or greater were identified, with baseline characteristics noted in Table 1. The median OS of the entire cohort was 10 months (95% CI = 2.35-17.65 months). The median OS for patients 75 and older was 8 months vs. 10 months for patients aged 65-75 (p = 0.14). The median OS for patients with an ECOG of 1 was 13 months vs. 3 months for patients with an ECOG of 2 (p = 0.34). The median OS for patients receiving ICI as first line therapy was 18 months vs. 7 months for those receiving ICI as second line therapy or beyond (p = 0.11). The median OS for patients with PD-L1 expression 50% of greater was 10 months vs. 11 months for patients with PD-L1 expression less than 50% or unknown (p = 0.55). The median PFS for patients receiving ICI as first line therapy was 9 months vs. 2 months for those receiving ICI as second line therapy or beyond (p = 0.03). Eight (17%) patients had grade III/IV toxicity (3 pneumonitis, 1 CNS toxicity, 1 skin toxicity, 1 nephritis, 1 diarrhea, 1 hepatitis), and 8 patients (17%) received glucocorticoids related to their irAEs. Sixteen patients (33%) required hospitalization during treatment. Conclusions Our study demonstrates the efficacy and safety of immunotherapy in elderly patients with NSCLC compared to cohorts in contemporary clinical trials. In our population, patients aged 75 or greater receiving immunotherapy did not have significantly lower overall survival compared to patients aged 65-75. Treatment was generally well-tolerated with 17% of patients developing grade III/IV toxicity. Citation Format: Jacob Ripp, Ghulam R. Mohyuddin, Mohammed Al-Jumayli, Chao Huang. Outcomes in elderly patients with non-small-cell lung cancer receiving immune checkpoint inhibitor therapy: A real world experience [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2026.
Ploidy Levels and Fitness-Related Traits in Purebreds and Hybrids Originating from Sterlet ( Acipenser ruthenus) and Unusual Ploidy Levels of Siberian Sturgeon ( A. baerii)

The present study aimed to investigate and compare fitness-related traits and ploidy levels of purebreds and hybrids produced from sturgeon broodstock with both normal and abnormal ploidy levels. We used diploid Acipenser ruthenus and tetraploid A. baerii males and females to produce purebreds and reciprocal hybrids of normal ploidy levels. Likewise, we used diploid A. ruthenus and tetraploid A. baerii females mated to pentaploid and hexaploid A. baerii males to produce hybrids of abnormal ploidy levels. Fertilization of ova of A. ruthenus and A. baerii of normal ploidy with the sperm of pentaploid and hexaploid A. baerii produced fully viable progeny with ploidy levels that were intermediate between those of the parents as was also found in crosses of purebreds and reciprocal hybrids of normal ploidy levels. The A. ruthenus × pentaploid A. baerii and A. ruthenus × hexaploid A. baerii hybrids did not survive after 22 days post-hatch (dph). Mean body weight and cumulative survival were periodically checked at seven-time intervals. The recorded values of mean body weight were significantly higher in A. baerii × pentaploid A. baerii hybrids than other groups at three sampling points (160, 252 and 330 dph). In contrast, the highest cumulative survival was observed in A. baerii × A. ruthenus hybrids at all sampling points (14.47 ± 5.70 at 497 dph). Overall, most of the studied sturgeon hybrids displayed higher mean BW and cumulative survival compared to the purebreds. The utilization of sturgeon hybrids should be restricted to aquaculture purposes because they can pose a significant genetic threat to native populations through ecological interactions.
Public Discourse Against Masks in the COVID-19 Era: Infodemiology Study of Twitter Data.

Background: Despite scientific evidence supporting the importance of wearing masks to curtail the spread of COVID-19, wearing masks has stirred up a significant debate particularly on social media. Objective: This study aimed to investigate the topics associated with the public discourse against wearing masks in the United States. We also studied the relationship between the anti-mask discourse on social media and the number of new COVID-19 cases. Methods: We collected a total of 51,170 English tweets between January 1, 2020, and October 27, 2020, by searching for hashtags against wearing masks. We used machine learning techniques to analyze the data collected. We investigated the relationship between the volume of tweets against mask-wearing and the daily volume of new COVID-19 cases using a Pearson correlation analysis between the two-time series. Results: The results and analysis showed that social media could help identify important insights related to wearing masks. The results of topic mining identified 10 categories or themes of user concerns dominated by (1) constitutional rights and freedom of choice; (2) conspiracy theory, population control, and big pharma; and (3) fake news, fake numbers, and fake pandemic. Altogether, these three categories represent almost 65% of the volume of tweets against wearing masks. The relationship between the volume of tweets against wearing masks and newly reported COVID-19 cases depicted a strong correlation wherein the rise in the volume of negative tweets led the rise in the number of new cases by 9 days. Conclusions: These findings demonstrated the potential of mining social media for understanding the public discourse about public health issues such as wearing masks during the COVID-19 pandemic. The results emphasized the relationship between the discourse on social media and the potential impact on real events such as changing the course of the pandemic. Policy makers are advised to proactively address public perception and work on shaping this perception through raising awareness, debunking negative sentiments, and prioritizing early policy intervention toward the most prevalent topics.
The Role of Fear in the Founding of the United States: A Historical and Philosophical Perspective

This chapter employs a historical, philosophical, and neuroscientific lens to explore the role of fear in the founding father’s construction of founding documents to include the US Constitution and its subsequent deleterious impact on society. Fear translated to intentional exclusion of entire cohorts (racial/ethnic minorities/women) of the US population that later had to be reconciled through a series of amendments to the US Constitution.
Earnings management in the short- and long-term post-regulation periods

We examine the change in the level and significance of accrual and real earnings management over the period 1996–2018. Our univariate results show that both accrual and real earnings management continue to persist, although they have significantly decreased over time. After controlling for significant factors that have been shown to affect earnings management, we find that both accrual and real-activities earnings management have significantly decreased in the short term after the regulations, but accrual earnings management reverted back to its pre-regulation levels in the long run. Further, contrary to the findings of prior research (e.g., Cohen et al. in Account Rev 83:757–787, 2008) that managers have shifted away from accruals to real earnings management in the short-term post-regulation period, we find evidence that firms actually reduced real earnings management both in the short- and long-term post-regulation periods. The results are robust to alternative sample designs and inclusion of additional control variables, and go against the widely held beliefs that accruals-based earnings management is significantly less prevalent now than it used to be.
Registered Nurses' Experiences With Incivility During the Early Phase of COVID-19 Pandemic: Results of a Multi-State Survey.

Background:Incivility among workers in the health sector is recognized as an occupational hazard. The COVID-19 outbreak brought sudden and profound changes to many health care settings, many of whi...
Proposal for the Development of Social Responsibility and Professional Ethics in the Computer Engineering Curriculum

This paper describes a proposal for the development of Professional Ethics and Social Responsibility in the field of computer engineering, with the aim of contributing with a plan for concrete action to the general discussion space that is being addressed by the academic about the social role of technologies in our time. A model based on competency-based training is proposed to develop these essential concepts in the computer scientists’ professional training among programs within interdisciplinary areas so that they allow the development of Professional Ethics and Social Responsibility through a natural link with the technical tools and methods of the discipline itself. A computer engineering program is taken as an example and the project proposal is described based on objectives, courses, learning results and methodological strategies to create an experience related to Professional Ethics and Social Responsibility for students through studied cases of real problems that are analyzed within the specific technical field and the inherent social field.
CIVIL PRACTICE Civil Practice Act: Disallow Waiver of Disqualification of Court Reporter for Interest; Disallow Continuing Contracts for Court Reporting Services

The Act prohibits the waiver of disqualification of financially interested court reporters and requires disclosure by the reporter of the financial arrangement between the reporter and the party paying for the reporting services. The Act prohibits continuing contracts fro court reporting services. The Act also provides penalties for violations of the Act.
Production of testosterone by prostate and other peripheral tissues in man.

Publisher Summary This chapter describes the production of testosterone by prostate and other peripheral tissues in man. The major circulating androgens in adult men are testosterone, dihydrotestosterone, androstanediol, and androstenediol. The concentrations are such that the net androgenicity of plasma stemids in men is chiefly a function of plasma testosterone concentration. It is found that only when plasma testosterone concentration reaches the hypogonadal range could the other steroids exert significant androgenic effects. Tissue extraction is determined both by the rate of steroid transport from plasma and by the rate of enzymic metabolism in the cells. The transport of steroids from plasma is in turn influenced by steroid binding to plasma proteins. In normal men, over 95% of the testosterone production rate of 7 mg daily is a result of Leydig cell secretion. Testosterone precursors thus contribute little to the production rate. Dehydroepiandrosterone is secreted primarily by the adrenal cortex, both free and as the sulfate, and small amounts are secreted by the ovary and by the testis. The only possible precursor of dehydroepiandrosterone is 17-hydroxypregnenolone; the transfer factor is so low that it can be ignored.
Are time-averaged restraints necessary for nuclear magnetic resonance refinement?: A model study for DNA

Abstract A recently suggested method for refinement of structural data obtained from two-dimensional nuclear magnetic resonance experiments using molecular dynamics (MD) is explored. In this method, the time-averaged values of the appropriate internal co-ordinates of the molecule, calculated from the MD trajectory, are driven by restraints towards the experimental target values. This contrasts with most refinement procedures currently in use, where restraints are applied based on the instantaneous values of the appropriate co-ordinates. Both refinement methods are applied to the EcoRI restriction site DNA hexamer d(GAATTC)2, using target nuclear Overhauser enhancement distances derived from a one nanosecond unrestrained MD simulation of this structure. The resulting refined structures are compared to the results of the unrestrained MD trajectory, which serves as our “experimental” data. We show that although both methods can yield an average structure with the correct gross morphology, the new method allows both a much more realistic picture of inherent flexibility, and reproduces fine conformational detail better, such as sequence dependency. We also analyze the very long MD trajectory generated here (longer than any previously reported for a DNA oligomer), and find that significantly shorter simulations, typical of those frequently performed, may not yield acceptably reliable values for certain structural parameters.
Investment, Financing Decisions, and Tax Policy

Studies of tax policy and corporate investment have been prominent in public finance and macroeconomic research. By integrating corporate income tax rates, investment tax credits, and the value of depreciation allowances into the "cost of capital," economists have analyzed the effects of taxes on capital spending. Most studies assume that firms respond to prices set in centralized securities markets, such as market interest rates of Tobin's q, and firms undertake all profitable investment projects. Firms choose the mix or finance among internal funds, debt, and new equity independently; the availability of finance does not limit investment. The implications for tax policy are clear: the marginal tax rate on returns from a new project matters for investment, not the firm's average tax burden on returns from its investments in place. For firms that face imperfect markets for external finance, however, it is no longer sufficient to focus only on the cost of funds determined in centralized securities markets. In particular, if the cost of internal finance differs substantially from external finance for some firms, their investment depends on available cash flow. For these firms, the amount of earnings devoted to taxes - and therefore the average tax rate on returns from existing projects - matters for investment, possibly along with incentive effects of marginal tax rates. We build on recent research that analyzes asymmetric information between firms and suppliers of external capital to examine the link between finance and investment, and, correspondingly, the role played by average as opposed to marginal tax rates in the investment process. Our approach emphasizes firm heterogeneity; some firms can obtain low-cost external funds to respond completely to signals from centralized securities markets, while internal finance constrains the investment of others. In Sections I and II, we consider a q investment model for two types of firms: (i) firms that face essentially no cost disadvantage of external finance, and (ii) firms that must pay a significant premium to raise funds from external sources because of information asymmetries. In both cases, we evaluate the relative influence of average and marginal tax rates on investment. Section III summarizes empirical evidence on the link between internal finance and investment across heterogeneous groups of firms. Section IV concludes and discusses implications for tax policy.
Resistance to D-cycloserine in the tubercle bacilli: mutation rate and transport of alanine in parental cells and drug-resistant mutants

A single transport system was found to accumulate l- and d-alanine, glycine and d-serine in Mycobacterium tuberculosis. The results of inhibition experiments suggested that the antibiotics d-cycloserine and O-carbamyl-d-serine were also transported by the alanine-glycine-d-serine system. A d-cycloserine-resistant permease-competent (d-CS(r)/perm(+)) mutant and a d-cycloserine-resistant permease-defective (d-CS(r)/perm(-)) mutant were isolated. The d-CS(r)/perm(-) mutant was not found to be more resistant to the drug than was the d-CS(r)/perm(+) mutant. The data were consistent with the conclusion that resistance to d-cycloserine in the tubercle bacilli is primarily due to mutations in the gene(s) controlling the enzyme d-alanyl-d-alanine synthetase. The mutation rate was calculated to be about 10(-10) mutations per bacterium per generation.
A partial amino acid sequence of α lactalbumin I of the grey kangaroo (Macropus giganteus)

Two types of α-lactalbumin were separated chromatographically from the milk of the grey kangaroo and were found to have very similar amino acid compositions. Analysis of one type resulted in elucidation of the sequence of 42 residues from the NH2 terminus of the molecule. Only 7 of the first 22 residues in the kangaroo molecule were identical with corresponding residues in either of three α-lactalbumins from other mammalian species. The sequence from residues 23 to 42 in the kangaroo protein is very similar to the other α-lactalbumin sequences. There is also considerable sequence similarity between kangaroo α-lactalbumin and human and chicken lysozymes. Other structural features, however, appear to be unique to kangaroo α-lactalbumin. Comparison of the sequences of the α-lactalbumins from the kangaroo, man, cow, and guinea pig with those of human and chicken lysozyme give additional insight into the evolutionary relationships of these proteins as well as the structural basis of α-lactalbumin function.
Double-Loop Learning and the Global Business Student

In preparing students for employment in commerce, the student needs to be aware of many aspects not necessarily included in business programs. In recognizing students often have no or limited exposure to foreign environments, the authors developed an electronic exchange between students in Canada and Kazakhstan. In this exchange, students not only learned about foreign marketplaces but were able to integrate classroom teachings and text knowledge into their actions. This approach resulted in enhanced learning for students through double-loop processes and development in their other courses.
A study of dynamic aspects related to voltage collapse in power systems

The applicability of the multiparameter stability theory proposed in a book by K. Huseyin (1975) to the study of voltage stability in power systems is explored. The methodology is based on the eigenvalues of the Jacobian matrix, evaluated at an arbitrary equilibrium point in the vicinity of a singular point (or critical point), and an asymptotic equation of the equilibrium surface (path) around this point is obtained through a systematic multiparameter perturbation technique. The technique provides surface (path) derivatives, which are used to construct the equilibrium surface (path). It is applied to a power system dynamic model which includes load dynamics. >
Notch Signaling Pathway in Ovarian Cancer

The literature is replete with reports of the paradoxical role of Notch signaling in human cancer. Notch appears to act as both an oncogene and a tumor suppressor gene depending on the cellular context. This review focuses on the nascent knowledge of Notch signaling in ovarian cancer. Despite advances in chemotherapy and radical surgery, ovarian cancer remains the most deadly gynecologic malignancy. Therapeutic improvements are necessary to enhance outcomes of patients with ovarian cancer. I will review the evidence for Notch activation in ovarian cancer and potential strategies for Notch inactivation as targeted treatment of ovarian cancer.
On the site of pentylenetetrazol-induced enhancement of auditory responses of the reticular formation: Localized cooling and electrical stimulation studies

Abstract Pentylenetetrazol (PTZ), administered systemically, extensively enhanced the auditory responses of neurons of the mesencephalic reticular formation (MRF). Responses evoked in the mesencephalic reticular formation by electrical stimuli in several primary auditory nuclei (cochlear nucleus, superior olivary complex and lateral lemniscus, but not inferior colliculus) were also enhanced by pentylenetetrazol in the majority of cases. Bilateral cryoprobe cooling in the lateral lemniscal tract substantially reduced the auditory-evoked field potentials (EPs) in the mesencephalic reticular formation before and after administration of pentylenetetrazol. Cooling in the inferior colliculus (IC) produced a small reduction in auditory-evoked field potentials in the mesencephalic reticular formation before drug but a more substantial degree of reduction after administration of pentylenetetrazol. A relatively small degree of pentylenetetrazol-induced enhancement of the response was seen in neurons of the inferior colliculus (158% of control) as compared to that of neurons in the mesencephalic reticular formation (410%). These findings would be consistent with the reported ability of pentylenetetrazol to block presynaptic inhibition if the input from the inferior colliculus to the mesencephalic reticular formation has inhibitory as well as excitatory components. These data along with the present authors' recent finding of enhancement of response with microapplication of convulsants strongly suggest that enhancement of responses of neurons of the mesencephalic reticular formation, induced by systemically administered convulsants such as pentylenetetrazol is exerted, to a large extent, by direct actions on synaptic elements of the reticular formation.
Choices in Cataloging Electronic Journals.

Abstract Libraries and catalogers face choices in the treatment of the growing collections of electronic journals. Policies issued by CONSER and the Library of Congress allow libraries to edit existing print records to accommodate information pertaining to the electronic versions (single record option) or to create new records for them. The discussion describes each option and considers the advantages and disadvantages of both choices.
Vitamin B12 deficiency associated with disease of the small intestine. Observations on an infant following extensive small bowel resection.

Summary Evidence is reviewed indicating that vitamin B 12 is absorbed in the lower part of the small intestine in man. Cases of megaloblastic anemia related to intestinal disease are usually associated either with stasis of intestinal contents or with a defect in the absorptive function of the lower small intestine. The former group responds to therapy which relieves stasis or to broad-spectrum antibiotic treatment. The latter group responds to medical therapy improving the absorptive function of the affected bowel. A case of megaloblastic anemia developing after a massive resection of small intestine in a newborn baby is presented. A case such as this requires long-term intramuscular therapy with vitamin B 12 .
Ventricular Activation And Repolarization Viewed By Images Of Voltage-Sensitive Dyes

Patterns of activation (A) and perhaps repolarization (R) depend on myocardial fiber structure and intercellular resistance, parallel and perpendicular to fiber orientation. Gray scale maps of A and R were measured from Langendorff preparations of left guinea pig ventricles stained with a voltage-sensitive dye (di-4-ANEPPS). Action potentials (124) were recorded from syncytia (6x6 and 12x12 mm) under SA node control, or stimulated at the edges (4) of a patch viewed with a photodiode array. At the end of the runs, muscles were marked with ink, fixed, sectioned every 5 pm as a function of depth, up to 1 mm. Fiber axis rotated less than 15 degrees in depth for the first 0.5 mm of epicardium and was aligned with respect to optical maps of A and R. Fast and slow A pathways matched respectively the parallel and perpendicular orientations of the fiber axis. R did not follow the fast axis of fiber orientation, but appears to travel either transverse or 45 degrees to it. R typically occurred at the apex of the ventricle suggesting that these cells have intrinsically shorter action potential durations (APD's). Under SA node control, Purkinje fibers accelerated the conduction velocity of the A process 4 fold over electrical pacing. The average velocity of R, however, remained the same whether SA node or electrically paced, demonstrating that Purkinje fibers do not drive the R process. During hypoxia, A patterns and conduction velocity remained stable, but APD's decreased dramatically within 10 minutes and the pattern of R become random and its velocity decreased. Thus R is also an active process, dependent on cell-to-cell coupling and highly susceptible to hypoxia.
Association of prior infection with Chlamydia pneumoniae and angiographically demonstrated coronary artery disease

Objective. —To evaluate the association between prior infection withChlamydia pneumoniae, as measured by IgG antibody, and coronary artery disease. Design. —A population-based, case-control study. Setting. —Group Health Cooperative of Puget Sound, a Seattle-based health maintenance organization. Participants. —Men 55 years of age and younger and women 65 years of age and younger. Cases (n=171) were members of Group Health Cooperative undergoing diagnostic coronary angiography who had at least one coronary artery lesion occupying 50% or more of the luminal diameter. The population controls (n=120) were Group Health Cooperative members without known coronary heart disease. Main Outcome Measure. —The adjusted odds ratio (OR) for coronary artery disease associated with priorCpneumoniaeinfection as measured by the presence of IgG antibody. Results. —After adjusting for age, gender, and calendar quarter of blood drawing, the OR for coronary artery disease associated with the presence of antibody was 2.6 (95% confidence interval, 1.4 to 4.8). The association was limited to cigarette smokers, in whom the OR was 3.5 (95% confidence interval, 1.7 to 7.0). Among never-smokers, the OR was 0.8 (95% confidence interval, 0.3 to 1.9). When cases and controls were restricted to those assayed concurrently, the adjusted OR (smokers and nonsmokers combined) was 4.2 (95% confidence interval, 1.8 to 10.0). Adjustment for serum cholesterol, hypertension, alcohol use, diabetes, and socioeconomic status did not change these results. Only a weak association was found when cases were compared with 63 subjects whose angiographic results were normal (OR, 1.2; 95% confidence interval, 0.6 to 2.2). Conclusions. —These results generally support the previously reported association betweenCpneumoniaeinfection and coronary heart disease. However, caution should be used in interpreting the basis for this association. (JAMA. 1992;268:68-72)
Concluding remarks I. Limnology now and in the future

On behalf of the officers and members of the Societas Internationalis Limnologiae, I wish to reiterate our heartfelt thanks for the initiation, organization, and execution of this informative and rewarding symposium. We of course acknowledge the long history of the University of Helsinki, now in its 350th year, as providing the necessary atmosphere conducive to development of educational and research programs. In hydro-biology, as in so many disciplines, education and research are inseparable, essential partners required by both to progress effectively.
Cobe Spectra is superior to Fenwal CS 3000 Plus for collection of hematopoietic stem cells

One hundred and seventy-seven stem cell apheresis procedures performed on 91 patients using the Fenwal CS 3000 Plus cell separator and 61 procedures performed on 37 patients using the Cobe Spectra cell separator were studied to compare the CD34+ cell collection efficiencies (CE; the proportion of the total CD34+ cell content in the blood volumes processed that is harvested) of the two machines. The absolute peripheral blood CD34+ cell count was comparable for the two groups (P = 0.27). A strong correlation was seen between the blood CD34+ cell count and the total number of CD34+ cells collected for the Spectra (r2 = 0.59; P < 10−6) and for the CS 3000 Plus (r2 = 0.60; P < 10−6). No significant correlation emerged between the peripheral blood CD34+ cell count and the CE of either machine. The total number of CD34+ cells collected per procedure was comparable (P = 0.51): median 113 × 106 for CS 3000 Plus and median 218 × 106for Spectra. CE was significantly higher with the Spectra (median 45.7%, range 9.8–98.6%) than the CS 3000 Plus (median 30.3%, range 1.7–89.3%; P < 0.00001). We conclude that the CD34+ cell CE of the Spectra is superior to that of the CS 3000 Plus. Therefore, under the usual clinical conditions, Cobe Spectra should be used preferentially for peripheral blood progentor cell collection to maximize the number of hematopoietic stem cells collected.