cssi/SciSciGPT-SciSciNet huggingface dataset:
Depletion of cardiac norepinephrine in rats and mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a commercially available chemical reagent. Although little has been known about its biological effects, recently MPTP has been reported to cause irreversible Parkinson's disease-like symptoms in humans and in monkeys. We describe here another pharmacologic effect of MPTP, the ability to deplete cardiac norepinephrine in rats and mice. In mice, cardiac norepinephrine concentration decreased within 1 hr, was maximally depleted at 24 hr, and recovered by 4-7 days after i.p. injection of a 32 mg/kg dose of MPTP. The depletion was antagonized by desipramine pretreatment, as was norepinephrine depletion by tyramine. In rats, cardiac norepinephrine depletion by 10-30 mg/kg, i.p., doses of MPTP was accompanied by depletion of cardiac dopamine and of norepinephrine in the mesenteric artery. In rats and in mice, norepinephrine in brain was affected to a smaller degree than was norepinephrine in heart, and dopamine in brain was depleted very little if at all. In spontaneously hypertensive rats, the depletion of cardiac norepinephrine was associated with a marked antihypertensive effect. The p-hydroxy analog of MPTP did not deplete cardiac norepinephrine in rats, indicating that its possible formation as a metabolite of MPTP was not involved in the depletion of cardiac norepinephrine. These findings extend the spectrum of known pharmacologic effects of MPTP.
Model for the Pion-Pomeranchon Regge Cut in the Neutron-Proton Charge-Exchange Reaction

A model is developed in which the pion-Pomeranchon Regge cut in the $\mathrm{np}$ charge-exchange reaction is calculated from the Mandelstam diagram. We find that the Regge cut is self-conspiratory, and is determined by two parameters besides those associated with the pion pole and the Pomeranchon. The sharp forward peak is reproduced through the destructive interference between the pole and the cut. An excellent fit is obtained in the small-$t$ region, and the values of the parameters producing this fit agree with physical intuition.
Accurate Distance Constraints for RNA Structures Using Deer Spectroscopy

Understanding structure-function relationships in RNA and RNA-protein complexes requires robust methods for obtaining structural information on a variety of length scales. DEER (double electron-electron resonance) is emerging as a powerful method for very accurate (± 2 A over 15-80 A) distance measurements between pairs of nitroxide labels that can be placed using several available conjugation sites in RNA nucleobases or phosphodiester linkages. Here, we show the potential for DEER spectroscopy in monitoring global RNA folding and also small changes in RNA structure within a model system that is based on the Hammerhead ribozyme. This catalytically active RNA, a three-helix junction motif with a buried active site, undergoes cation-dependent folding transitions that are linked to activity. Nitroxide labels placed at strategic positions allow helix-docking and active-site core rearrangements to be monitored by measuring the dipolar coupling between paramagnetic sites. This poster will present the results of DEER measurements obtained at both X-band and Q-band, where the higher-frequency Q-band spectroscopy significantly enhances the sensitivity of this technique. Mg2+-dependent global folding, and evidence for a smaller local structural change with higher added metal concentrations, are both observed in this RNA. Since labels can be placed at targeted sites within both nucleic acids and proteins, and there is no inherent limitation on macromolecular size, DEER spectroscopy has potential for obtaining high-resolution structural information in complex RNAs and in large RNA or DNA-protein complexes.
Volunteer Bias and the Five-Factor Model

We correlated consent granting for release of standardized test scores and willingness to be followed up in longitudinal research with measures of the five-factor model of personality in introducto...
Presence of 4‐hydroxynonenal in cerebrospinal fluid of patients with sporadic amyotrophic lateral sclerosis

A marker of lipid peroxidation 4-hydroxynonenal (HNE) was elevated in the cerebrospinal fluid (CSF) of a patient with sporadic amyotrophic lateral sclerosis (sALS) compared with that of most patients with other neurological diseases. Such elevations of HNE were sufficient to kill cyclic adenosine monophosphate (cAMP)-differentiated motor neuron hybrid cells in vitro, and anti-oxidants prevented this HNE-dependent cell death. These data suggest that oxidative stress and lipid peroxidation are associated with and may promote motor neuron degeneration in sALS.
Cross-linking dendrimers with allyl ether end-groups using the ring-closing metathesis reaction.

A third generation Frechet-type dendrimer containing 24 allyl ether end-groups was synthesized, cross-linked using the ring-closing metathesis (RCM) reaction, and the core was removed hydrolytically without significant fragmentation. The results are analogous to those previously reported for homoallyl ether dendrimers (Wendland, M. S.; Zimmerman, S. C. J. Am. Chem. Soc. 1999, 121, 1389−1390) suggesting that the less readily available homoallyl ether dendrimers can be replaced by their allyl ethers analogues in a range of applications.
Use of recombinant calpain-2 siRNA adenovirus to assess calpain-2 modulation of lung endothelial cell migration and proliferation.

In this study, we developed an adenoviral vector harboring calpain-2 siRNA expression unit in which sense and anti-sense strands composing the siRNA duplex were connected by a loop and transcribed into a siRNA in porcine pulmonary artery endothelial cells (PAEC). We screened one efficient adenoviral vector Ad/si-m187 and found that Ad/si-m187 successfully exerted a gene knockdown effect on calpain-2 mRNA transcription and protein expression levels. The protein content of calpain-2 was reduced by 30%–80% in PAEC infected with Ad/si-m187 in comparison to a control adenoviral vector Ad/si-luc. The mRNA levels of calpain-2 were measured by real-time PCR and were decreased by 60%–100% and in a dose dependent manner. In correspondence to silencing calpain-2 gene expression, calpain-2 activity was decreased significantly. We further evaluated the role of calpain-2 in endothelial cell migration and proliferation. PAEC infected with Ad/si-m187 displayed impaired migration and cell proliferation in comparison to cells infected with control adenoviral vector (Ad/si-luc). These results indicate that adenoviral vector harboring calpain-2 siRNA expression unit is a valuable tool to study the biology of calpains and that calpain-2 plays an important role in lung endothelial cell migration and proliferation.
Accrual Accounting and Library Materials Acquisitions

The purpose of this report is to provide information about the accrual method of Financial accounting for non‐profit organizations, to explain who uses the accrual method and why, and to determine if it poses a problem in managing the business of library acquisitions. This report is in response to concerns raised by acquisitions librarians regarding the uses and interpretations of accrual accounting methods at some institutions. In addition, it includes discussions of the possible ramifications accrual accounting methods can have on the process of acquiring selected library materials, such as serials and standing orders.
Evidence for leukotriene A4 as an intermediate in the conversion of 5-HPETE to leukotriene B4 catalyzed by cytochrome P-450

Hydrolysis of 5-hydroperoxyeicosatetraenoic acid catalyzed by cytochrome P-450 in the absence of NADPH formed a product with spectral and HPLC characteristics identical with those of leukotriene B4, 5(S),12(R)-dihydroxy-6-cis,8,10-trans,14-cis-eicosatetraenoic acid (LTB4). The product mixture suggests that trans-5,6-oxido-7,9-trans,11,14-cis-eicosatetraenoic acid, leukotriene A4 (LTA4) is an intermediate in the reaction. We suggest that the formation of LTB4 with the essential 6-cis stereochemistry is due to tight binding of the 5-HPETE to the cytochrome P-450 at a site that does not allow it to isomerize to the kinetically favored 6,8,10-trans configuration during attack of hydroxyl ion at C-12.
Autoimmune pancreatitis-related diabetes: quantitative analysis of endocrine islet cells and inflammatory infiltrate

In autoimmune pancreatitis (AIP), mechanism(s) of paradoxical glycemic control improvement (GCI) often occurring after pancreatic resection and steroid therapy are not fully elucidated. Using image quantitation, AIP cases (n = 10) with pre- and post-surgical glucose values were compared with chronic pancreatitis (CP) and normal pancreas (NP) regarding percent chromogranin immunohistochemistry (IHC) positivity as a surrogate marker of endocrine endowment; intra-islet T and B lymphocyte and plasma cell enumeration with CD3, CD20, and IgG4 IHC; and CD34 IHC islet vascularity quantitation. Postsurgical GCI, noted in 8/10 (80%) AIP cases, approached statistical significance (P = 0.07) compared to CP. Endocrine endowment reduction, noted by a lower percent of chromogranin + pancreatic parenchyma, was seen in AIP (4.54%) and CP (3.20%) compared to NP (7.95%); only the CP decrease was statistically significant (P = 0.02) since AIP often had ductular endocrine neogenesis. Regression suggested an inverse correlation between endocrine endowment and GCI in AIP (R = 0.62, P = 0.06). AIP islets were smaller and disrupted by inflammatory cell infiltration. Compared to CP, AIP islets had higher CD3 + and CD20 + cell densities. IgG4 + plasma cells were often present at a high density in AIP but typically preserved the islets. Intra-islet CD34 staining showed a lower average vascularity in AIP compared to NP (P = 0.05). This study reaffirms postsurgical GCI in AIP. Prominent intra-islet inflammation and decreased vascularity in AIP may contribute to diabetogenic effects. Endocrine cell neogenesis and relative islet preservation despite islet inflammatory infiltration may explain the paradoxical GCI in AIP.
Changing practice of coronary bypass surgery and its impact on early risk and long-term survival

Over the past 20 years, a steady evolution in cardiac surgical techniques for coronary bypass graft (CABG) surgery has occurred. Recent reports are refining our knowledge of early and late survival after CABG surgery. Studies have documented the changing importance of well-recognized risk factors. New models that take into account multiple factors and that predict early risk of CABG surgery with good reliability have been developed. Long-term survival has been related to factors such as age, gender, diabetes mellitus, race, smoking history, left ventricular function, estrogen treatment in women, and serum lipids. Several recent studies provide insight into decision making regarding CABG versus catheter interventions for both primary and secondary revascularization. Data concerning new techniques, such as minimally invasive surgery, document promising results but also the anticipated learning curve of new procedures. Overall, favorable short-term and long-term survival results after CABG surgery continue to be reported despite an increasing elderly and complex patient group undergoing cardiovascular surgical procedures.
Seasonal abundance and vertical distribution of crab larvae in Delaware Bay

Larvae of 15 species or genera of crabs were collected and identified during a six month (May 26 to October 28, 1978) study in the mouth of Delaware Bay. Seasonal abundance and vertical distribution of each species were investigated. Most species studied had peak abundance in July and August except forCancer irroratus andOvalipes ocellatus which showed peak occurrence in May and June, respectively. Larvae of species strongly dependent on estuarine habitats, such asUca spp.,Pinnixa chaetopterana, andP. sayana, showed a tendency to congregate in near-bottom waters where net flow of water is landward, thus favoring retention within the estuary. Larvae ofOvalipes ocellatus, Cancer irroratus, andCallinectes sapidus were more common at the surface. This vertical distribution suggests that these larvae are flushed out of the estuary. The mechanisms of recruitment and replenishment of adult populations within the estuary would therefore depend on migration of megalopa and juveniles. *** DIRECT SUPPORT *** A01BY019 00006
HLA desensitization with bortezomib in a highly sensitized pediatric patient.

The proteasome inhibitor bortezomib has been used with variable success in the treatment of AMR following heart transplant. There is limited experience with this agent as a pretransplant desensitizing therapy. We report a case of successful HLA desensitization with a bortezomib-based protocol prior to successful heart transplantation. A nine-yr-old boy with dilated cardiomyopathy, not initially sensitized to HLA (cPRA of zero), required three days of ECMO, followed by implantation of a Heartmate II LVAD. Within six wk, the patient developed de novo class I IgG and C1q complement-fixing HLA antibodies with a cPRA of 100%. Two doses of IVIG (2 g/kg) failed to reduce antibody levels, although two courses of a novel desensitization protocol consisting of rituximab (375 mg/m(2) ), bortezomib (1.3 mg/m(2) × 5 doses), and plasmapheresis reduced his cPRA to 0% and 87% by the C1q and IgG assays, respectively. He underwent heart transplantation nearly two months later. The patient is now >one yr post-transplant, is free of both AMR and ACR, and has no detectable donor-specific antibodies by IgG or C1q. Proteasome inhibition with bortezomib and plasmapheresis may be an effective therapy for HLA desensitization pretransplant.
Effect of tyrosine kinase inhibition on basal and epidermal growth factor-stimulated human Caco-2 enterocyte sheet migration and proliferation.

Mucosal healing requires enterocyte migration (restitution) supplemented by proliferation. Proliferation and migration may be studied independently by thymidine uptake and proliferation-blocked cell migration using human Caco-2 enterocyte monolayers in culture. Since epidermal growth factor (EGF) promotes mucosal healing and the EGF receptor is a tyrosine kinase, we hypothesized that tyrosine kinases might therefore modulate enterocyte migration and proliferation. The tyrosine kinase inhibitors genistein and 2, 5-dihydroxymethylcinnamate, which block kinase ATP-binding and substrate-binding sites, respectively, were studied alone and with EGF. Proliferation was blocked with mitomycin. Although each inhibitor decreased basal and EGF-stimulated monolayer expansion when cell proliferation occurred, neither genistein nor 2, 5-dihydroxymethylcinnamate decreased migration when proliferation was blocked. However, each inhibitor prevented EGF stimulation of proliferation-blocked migration and thymidine uptake. More substantial inhibition of basal proliferation by genistein correlated with increased protein-linked DNA breaks, which may reflect nonspecific inhibition of DNA topoisomerase activity by genistein. The more specific 2,5-dihydroxymeth-ylcinnamate blocked changes in the α2 integrin subunit organization which may modulate EGF-stimulated migration. Antiproliferative effects of tyrosine kinase inhibitors decrease basal monolayer expansion but true basal enterocyte migration appears independent of tyrosine kinase regulation. However, a specific tyrosine kinase-dependent modulation of cell-matrix interaction inhibits EGF-stimulated migration. © 1994 Wiley-Liss, Inc.
Enhanced iris matching using estimation of in-plane nonlinear deformations

Like many visual patterns, captured images from the same iris biometric experience relative nonlinear deformations and partial occlusions. These distortions are difficult to normalize for when comparing iris images for match evaluation. We define a probabilistic framework in which an iris image pair constitute observed variables, while parameters of relative deformation and occlusion constitute unobserved latent variables. The relation between these variables are specified in a graphical model, allowing maximum a posteriori probability (MAP) approximate inference in order to estimate the value of the hidden states. To define the generative probability of the observed iris patterns, we rely on the similarity values produced by correlation filter outputs. As a result, we are able to develop an algorithm which returns a robust match metric at the end of the estimation process and works reasonably quickly. We show recognition results on two sets of real iris images: the CASIA database, collected by the Chinese Academy of Sciences, and a database collected by the authors at Carnegie Mellon University.
Titanium nitride as a diffusion barrier between nickel silicide and aluminum

The diffusion barrier properties of titanium nitride between nickel silicide and aluminum have been investigated in NiSi Schottky contacts on silicon for annealing temperatures of 400–600°C. No interaction between the metals of the contact structure was detected by backscattering spectrometry, even at 600°C. The electron barrier height of Schottky diodes stays constant at ϕBn = 0.67 ± 0.01 upon thermal annealing in vacuum at 500°C for 2 h . The ideality factor is n = 1.01. After 4 h, ϕ Bn decreases by about 10 mV and n rises to 1.0 6. The diodes degrade after annealing at 550°C or 600°C for 30 min.
Multiple molecular forms of cytoplsmic glycerol-3-phosphate dehydrogenase in rat liver

Two major zones of cytoplasmic l -glycerol-3-P dehydrogenase (EC 1.1.1.8) activity appeared in polyacrylamide gel isoelectric focusing analysis of homogenates of livers from rats weighing 300–350 g. At least three other minor zones of activity were also observed. The more anionic of the two major zones of activity does not appear in homogenates of livers from smaller rats but can be generated in vitro by storing the homogenates overnight at 4°. Liver homogenates could be resolved into three zones of activity by DEAE-Sephadex column chromatography. Two of these isoenzymic forms of the enzyme were isolated at a high level of purity by a series of steps including a final column of DEAE-Sephadex and were characterized by amino acid analysis. One of these two forms was indistinguishable from the single major form of the enzyme isolated and characterized from livers of smaller rats and corresponded to the more cationic of the two major forms of the enzyme observed by gel electrofocusing in this work. The second form isolated corresponded to the most cationic of the minor forms of the enzyme observed in gel electrofocusing. Alternative methods of smaple introduction into electrofocusing gels were employed including internal layering and injection, in addition to the usual polymerization of the sample throughout the gel.
In vitro synthesis of arachidonoyl amino acids by cytochrome c

Arachidonoyl amino acids are a class of endogenous lipid messengers that are expressed in the mammalian central nervous system and peripherally. While several of their prominent pharmacologic effects have been documented, the mechanism by which arachidonoyl amino acids are biosynthesized has not been defined. We have previously observed that the mitochondrial protein, cytochrome c, is capable of catalyzing the formation of the prototypic arachidonoyl amino acid, arachidonoyl glycine, utilizing arachidonoyl CoA and glycine as substrates, in the presence of hydrogen peroxide. Here we report that cytochrome c is similarly able to catalyze the formation of N-arachidonoyl serine, N-arachidonoyl alanine, and N-arachidonoyl gamma aminobutyric acid from arachidonoyl CoA and the respective amino acids. The identities of the arachidonoyl amino acid products were verified by mass spectral fragmentation pattern analysis. The synthetic reactions exhibited Michaelis-Menten kinetics and continued favorably at physiologic temperature and pH. Spectral data indicate that both cytochrome c protein structure and a +3 heme iron oxidation state are required for the reaction mechanism to proceed optimally. Reactions designed to catalyze the formation of N-arachidonoyl dopamine were not efficient due to the rapid oxidation of dopamine substrate by hydrogen peroxide, consuming both reactants. Finally, under standard assay conditions, arachidonoyl CoA and ethanolamine were found to react spontaneously to form anandamide, independent of cytochrome c and hydrogen peroxide. Accordingly, it was not possible to demonstrate a potential role for cytochrome c in the biosynthetic mechanism for either arachidonoyl dopamine or anandamide. However, the ability of cytochrome c to effectively catalyze the formation of N-arachidonoyl serine, N-arachidonoyl alanine, and N-arachidonoyl gamma aminobutyric acid in vitro highlights its potential role for the generation of these lipid messengers in vivo.
The proximo-distal spread of axonal degeneration in the dorsal columns of the rat.

The pivotal event in Wallerian degeneration is the breakdown of the axon. Establishing the pathophysiology of axonal degeneration has implications for the understanding of the pathogenesis of other types of nerve degenerations. A key aspect of the pathophysiology is the spatiotemporal pattern of spread after transection, an issue that has remained controversial. We have studied the progression of axonal degeneration in the dorsal columns of the rat following L4L5L6 dorsal radiculotomy. Axonal degeneration proceeds in a proximo-distal fashion, beginning near the site of transection and spreading up the dorsal columns at a net rate of about 3 mmh−1. In addition, there was early degeneration of the preterminal axons in the gracile nuclei. This pattern suggests that the ‘clearing’ of axonally transported materials from the distal stump by continued anterograde transport may underlie axonal breakdown after transection.
Magnitude scaling of the dependent variable in decompositional multiattribute preference models

The results of this study produced strong support for the validity magnitude scaling procedures when aggregate data are analyzed. For example, the cross modality matching procedures indicated the geometric means of the preference responses to the CMA stimuli were characterized by power functions with estimated exponents similar to the theoretically derived exponents. When the data were analyzed at the individual level, however, considerable heterogeneity across individuals was found--the power function exponents vary considerably from individual to individual. This heterogeneity across subjects is similar to the findings of previous research on magnitude scaling (Dawson 1982). This may, therefore be a major limitation of this scaling procedure in conjoint analysis applications because of the widespread use of conjoint analysis for the examination of individual respondent utility functions.
Sensitivity reduction in linear systems

A new measure of sensitivity with respect to initial conditions in linear multi-input time-varying systems is defined. Remarkable amongst its properties are its non-dependence on open-loop control and its invariance under a regular linear time-invariant transformation of the states. A system is shown to be less sensitive according to the new measure when driven by a feedback control, optimal with respect to a quadratic performance index, than when driven by any open-loop control. A relation between the control cost and the sensitivity measure is established, which aids in examining trade-off solutions in design procedures. An example illustrates the definition and the results.
Uptake and population-level impact of expedited partner therapy (EPT) on Chlamydia trachomatis and Neisseria gonorrhoeae: the Washington State community-level randomized trial of EPT.

Background Expedited partner therapy (EPT), the practice of treating the sex partners of persons with sexually transmitted infections without their medical evaluation, increases partner treatment and decreases gonorrhea and chlamydia reinfection rates. We conducted a stepped-wedge, community-level randomized trial to determine whether a public health intervention promoting EPT could increase its use and decrease chlamydia test positivity and gonorrhea incidence in women. Methods and Findings The trial randomly assigned local health jurisdictions (LHJs) in Washington State, US, into four study waves. Waves instituted the intervention in randomly assigned order at intervals of 6–8 mo. Of the state’s 25 LHJs, 24 were eligible and 23 participated. Heterosexual individuals with gonorrhea or chlamydial infection were eligible for the intervention. The study made free patient-delivered partner therapy (PDPT) available to clinicians, and provided public health partner services based on clinician referral. The main study outcomes were chlamydia test positivity among women ages 14–25 y in 219 sentinel clinics, and incidence of reported gonorrhea in women, both measured at the community level. Receipt of PDPT from clinicians was evaluated among randomly selected patients. 23 and 22 LHJs provided data on gonorrhea and chlamydia outcomes, respectively. The intervention increased the percentage of persons receiving PDPT from clinicians (from 18% to 34%, p < 0.001) and the percentage receiving partner services (from 25% to 45%, p < 0.001). Chlamydia test positivity and gonorrhea incidence in women decreased over the study period, from 8.2% to 6.5% and from 59.6 to 26.4 per 100,000, respectively. After adjusting for temporal trends, the intervention was associated with an approximately 10% reduction in both chlamydia positivity and gonorrhea incidence, though the confidence bounds on these outcomes both crossed one (chlamydia positivity prevalence ratio = 0.89, 95% CI 0.77–1.04, p = 0.15; gonorrhea incidence rate ratio = 0.91, 95% CI .71–1.16, p = 0.45). Study findings were potentially limited by inadequate statistical power, by the institution of some aspects of the study intervention outside of the research randomization sequence, and by the fact that LHJs did not constitute truly isolated sexual networks. Conclusions A public health intervention promoting the use of free PDPT substantially increased its use and may have resulted in decreased chlamydial and gonococcal infections at the population level. Trial Registration ClinicalTrials.gov NCT01665690
Beyond being an evaluator: The multiplicity of roles of the internal evaluator

The chapter explores critical roles of internal evaluators in contemporary organizational settings. The need is highlighted for an expanded, reconfigured, unorthodox set of roles and styles of work to meet the needs of the emerging learning organizations effectively. A discussion of major categories of internal evaluator roles emerged from the analysis of the evaluation literature and other sources suggests new directions for how internal evaluation is conceptualized and practiced. Systematic promoting and advancing positive change, evaluation capacity building, decision making, learning, and evaluative thinking in organizations are seen as part of the harmonized internal evaluator role. © Wiley Periodicals, Inc., and the American Evaluation Association.
Hypnotic suggestion and the histamine wheal

Abstract Recent articles by several British investigators report that the responses to skin test reactions in immediate and delayed hypersensitivity can be inhibited by direct suggestion under hypnosis. With the use of a standardized hypnotic technique, groups of normal, allergic, and urticarial subjects were given skin tests with histamine and ragweed, in an attempt to alter the whealing response. However, under the conditions of this experiment no significant change was observed.
Telephone survey to assess influenza-like illness, United States, 2006.

Although current national response plans assume that most influenza-infected patients would stay home during a pandemic, surveillance systems might be overwhelmed and unable to monitor their health status. We explored the feasibility of using a nationwide telephone survey to monitor at-home patients. Of randomly selected adults surveyed during low influenza activity months (April–October 2006, surveillance weeks 17–41), 86% (7,268/8,449) agreed to answer questions about health status and influenza-like illness symptoms. Three percent (230/7,628) self-reported “flu.” A subset (0.9%, 68/230) self-reported fever. In comparison, the Centers for Disease Control and Prevention’s Sentinel Provider Network reported clinical influenza-like illness rates of 1.2%, 0.9%, and 1.2% for weeks 17, 20, and 41, respectively. The consistency between information obtained by telephone and surveillance data warrants further studies to determine whether telephone surveys can accurately monitor health status during seasonal influenza peaks and to augment current surveillance systems during a pandemic.
A Randomized Study of the Safety and Immunogenicity of DTPa-HB-IPV Vaccine Administered as Three Doses or in a Sequential IPV/OPV Schedule at 2, 4, and 6 Months of Age ♦ 933

A Randomized Study of the Safety and Immunogenicity of DTPa-HB-IPV Vaccine Administered as Three Doses or in a Sequential IPV/OPV Schedule at 2, 4, and 6 Months of Age ♦ 933
Methemoglobinemia due to ingestion of N,N-dimethyl-p-toluidine, a component used in the fabrication of artificial fingernails

An acute cyanotic episode due to methemoglobinemia occurred in a 16-month old girl following the ingestion of N,N-dimethyl-p-toluidine, a commercially available component used in the production of artificial fingernails. The amount of the parent compound ingested was about 6 mg/kg of body weight. Administration of methylene blue was effective in the reversal of the methemoglobinemia. In vitro studies suggest that the activity of the compound was probably due to its biochemical transformation to the toxic metabolite p-methylphenylhydroxylamine. We expand the list of aromatic amino or nitro compounds and their derivatives capable of producing methemoglobinemia and call attention to the hazard of their ingestion.
Phenotypic spectrum of polycystic ovary syndrome: clinical and biochemical characterization of the three major clinical subgroups

Objective We tested the hypothesis that the three clinical phenotypes of polycystic ovary syndrome (PCOS) represent forms of the same metabolic disorder. Design Prospective cohort analysis. Setting University-based tertiary care. Patient(s) Three-hundred sixteen untreated consecutive women diagnosed as having PCOS. Intervention(s) None. Main Outcome Measure(s) Each subject underwent an evaluation of ovulatory function, body habitus, acne, and hirsutism; serum free and total testosterone (T), 17-hydroxyprogesterone (17-HP), and DHEAS; and fasting plasma glucose and insulin levels. Insulin resistance and β-cell function were assessed using the homeostatic assessment model equation (HOMA-IR and HOMA-β-cell, respectively). Result(s) The Oligo+HA+Hirsutism phenotype was present in 48% of subjects, Oligo+HA in 29%, and Oligo+Hirsutism in 23%. The three phenotypes did not differ in mean body mass index, waist-to-hip ratio, racial composition, degree of oligo-ovulation, prevalence of acne, or family history of hyperandrogenic symptomatology. However, subjects demonstrating the Oligo+HA+Hirsutism phenotype were the youngest and had the greatest degrees of hyperandrogenemia, hyperinsulinemia, and β-cell function; patients with the Oligo+Hirsutism phenotype where the oldest and had the mildest degrees of hyperandrogenemia, hyperinsulinemia, and β-cell function. Subjects with the Oligo+HA phenotype demonstrated intermediate degrees of hyperandrogenemia and metabolic dysfunction. Conclusion(s) We conclude that the three clinical phenotypes of PCOS do not represent forms of the same metabolic disorder and may be the result of varying degrees of metabolic dysfunction; greater degrees of β-cell function and circulating insulin levels favored the development of hirsutism and frank hyperandrogenemia.
Conformation of the cyclic tetrapeptide dihydrochlamydocin. Iabu-L-Phe-D-Pro-LX, and experimental values for 3 1 intramolecular hydrogen bonds by X-ray diffraction†

Chlamydocin, Iabu-L-Phe-D-Pro-LX, is a naturally occurring cyclic tetrapeptide that exhibits high cytostatic activity. The conformation of the peptide ring, as well as the stereo configuration in the vicinity of the epoxide ring, have been established by a single-crystal X-ray study of dihydrochlamydocin: C28H40N4O6·H2O. It crystallizes in the monoclinic space group P21 with a = 12.616(6) A, b = 12.355(6) A, c = 9.442(5) A, and β = 99.5(1)°. The structure was solved by the symbolic addition procedure for phase determination followed by the tangent formula method of phase refinement. This structure represents the first cyclic tetrapeptide in which all four peptide units have been found in the trans conformation; however, each peptide unit is significantly nonplanar with ω angles deviating by 14–24° from the ideal value of 180°. This molecule contains two intramolecular 3 1 hydrogen bonds and experimentally determined parameters for these seven-membered turns are presented.
Mechanisms of petroleum hydrocarbon toxicity: studies on the response of rat liver mitochondria to Prudhoe Bay crude oil and its aliphatic, aromatic and heterocyclic fractions.

Abstract The effect of Prudhoe Bay crude oil (PBCO) and its different fractions [aliphatic, aromatic, heterocyclic (NOS)] on the bioenergetic functions of isolated rat liver mitochondria were studied. A DMSO extract of PBCO inhibited state 3 respiration (in the presence of ADP) with either succinate or β-hydroxybutyrate as substrate. The ascorbate-TMPD dependent state 3 respiration was not affected. Succinate dehydrogenase and β-hydroxybutyrate dehydrogenase activities were also lost in the presence of the PBCO extract suggesting that inhibition of state 3 respiration may be due to blockage of the electron transport chain. Stimulation of state 4 respiration (in the absence of ADP) and of the oligomycin sensitive ATPase activity by the PBCO extract was observed. Fractionation of PBCO indicated that the aromatic fraction was mainly responsible for its inhibitory effects. By comparison, the heterocyclic fraction had weak inhibitory properties while the aliphatic fraction was essentially inactive. It is concluded that the aromatic components of PBCO inhibit mitochondrial respiration and oxidative phosphorylation mainly through impairment of the mitochondrial membrane and inhibition of β-hydroxybutyrate and succinate dehydrogenase supported electron transfer activities of the respiratory chain.
Comparing physicians on efficiency.

The appropriate way to measure physicians' efficiency is a matter of disagreement between those who pay for health care and those who provide it. Drs. Arnold Milstein and Thomas Lee write that shared understanding of differing perspectives on six key issues may speed convergence on a middle ground. Dr. Thomas Lee discusses the goals, stumbling blocks, and applications of quality and efficiency measurement.
Studies on troponin.

Abstract Troponin was isolated from preparations of the ethylene glycol bis-(β-aminoethyl ether)-N,N′-tetraacetic acid (EGTA)-sensitizing factor over the pH range of 3.5–4.6. The variations among troponins were due essentially to differences in the proportion and properties of the troponin A component. This was dictated by the choice of the source fraction (EGTA-sensitizing factor) and by the efficiency of recovery of troponin A in troponin by the isoelectric fractionation. A higher yield of troponin A was obtained at the alkaline edge of the given pH range. The relative proportion of troponin A in troponin was reflected by the A278 mμ:A260 mμ ratio and by the effect troponin had on the Mg2+-activated ATPase activity of synthetic actomyosin. The inhibitory effect of the EGTA-sensitizing factor on the Mg2+-activated ATPase activity of synthetic actomyosin in the presence of EGTA, was due to an interaction of troponin B and tropomyosin. Ultracentrifugal analysis revealed that this interaction was reflected by the formation of a hypersharp boundary different from the boundaries of troponin B or tropomyosin alone. Inhibition of the ATPase activity and complex formation was maximal at a ratio of tropomyosin to troponin B of approx. 1:1 (w/w). It is proposed that troponin A is responsible for the calcium sensitivity of the EGTA-sensitizing factor.
Methamphetamine-induced increases in putamen gray matter associate with inhibitory control.

Problematic drug use is associated with difficulty in exerting self-control over behaviors, and this difficulty may be a consequence of atypical morphometric characteristics that are exhibited by drug-experienced individuals. The extent to which these structural abnormalities result from drug use or reflect neurobiological risk factors that predate drug use, however, is unknown. The purpose of this study is to determine how methamphetamine affects corticostriatal structure and how drug-induced changes relate to alterations in inhibitory control. Structural magnetic resonance images and positron emission tomography (PET) scans, assessing dopamine D2-like receptor and transporter availability, were acquired in monkeys trained to acquire, retain, and reverse three-choice visual discrimination problems before and after exposure to an escalating dose regimen of methamphetamine (or saline, as a control). Voxel-based morphometry was used to compare changes in corticostriatal gray matter between methamphetamine- and saline-exposed monkeys. The change in gray matter before and after the dosing regimen was compared to the change in the behavioral performance and in dopaminergic markers measured with PET. Methamphetamine exposure, compared to saline, increased gray matter within the right putamen. These changes were positively correlated with changes in performance of methamphetamine-exposed monkeys in the reversal phase, and were negatively correlated with alterations in D2-like receptor and DAT availability. The results provide the first evidence that exposure to a methamphetamine dosing regimen that resembles human use alters the structural integrity of the striatum and that gray-matter abnormalities detected in human methamphetamine users are due, at least in part, to the pharmacological effects of drug experience.
Slow and fast markets

Abstract Informed traders need liquidity in order to profit from their private information. Markets provide liquidity and are compensated by the information released through trading. Fast markets provide access to a limit order book. Slow markets provide execution in an auction-based trading floor. Hybrid markets combine both execution venues. It is shown here that the overall efficiency of a hybrid market is determined by its fast component. The introduction of a trading floor does not generate more informed trading, only takes trading away from the fast market. Trading floors are thus inherently competitive to the fast market. We provide conditions that determine the competitiveness of a trading floor with respect to a fast market.
Pulsatile Versus Nonpulsatile Cardiopulmonary BypassNo Difference in Brain Blood Flow or Metabolism at 27°C

BACKGROUND It is unclear whether nonpulsatile perfusion adversely affects the brain. This study compared cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) betwen pulsatile and nonpulsatile cardiopulmonary bypass (CPB) in rabbits at 27 degrees C. METHODS In experiment A, 24 anesthetized New Zealand white rabbits underwent pulsatile CPB at 27 degrees C, using alpha-stat acid-base management. Animals were randomized to three groups based upon the duration of the period of systolic ejection (100, 120, 140 ms) and were perfused for 20 min at each of three pulse rates (150, 200, 250 pulse/min), generating nine arterial pressure waveforms. Arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (radiolabeled microspheres), and CMRO2 (Fick) were measured at the end of each 20-min period. In experiment B, 16 anesthetized rabbits were randomized to pulsatile (120-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 27 degrees C. AFter 1 h, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF and CMRO2 were measured. RESULTS In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all nine waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile bypass, 30 +/- 4 versus 32 +/- 5 ml.100 g-1.min-1, respectively. CMRO2 did not differ between pulsatile and nonpulsatile bypass, 1.7 +/- 0.2 versus 1.6 +/- 0.2 ml.100 g-1.min-1, respectively. CONCLUSIONS During CPB in rabbits at 27 degrees C, neither CBF nor CMRO2 is affected by flow character.
Modeling feeding and growth in Gulf of Alaska sockeye salmon: implications for high-seas distribution and migration

I analyzed data on stomach contents of sockeye salmon Oncorhynchus nerka and oceanographic variables collected during 1956 to 1964 in order to assess the spatial and temporal pat- terns of salmon feeding and growth in the Gulf of Alaska. A 2-stage statistical model was used to develop a feeding index, calculated as the product of feeding probability (assessed using the pres- ence/absence of gut contents of individuals collected at each site) and stomach fullness (prey weights transformed to account for temperature-dependent gastric evacuation and allometry). Combining these results with simple bioenergetic principles, I conclude that the reduction in salmon biomass during spring observed along the southern periphery of the Gulf can be explained by an equally sharp reduction in growth potential. This feature demarcates a region (between latitude 58 and 55° N) that is favorable to sockeye growth, as demonstrated by an order of magnitude change in salmon growth potential over a narrow range of sea surface temperatures (ca. 6 to 7°C). This pattern results from the combined effects of trends in feeding probability and stomach fullness across this temperature gradient. I documented a significant trend of larger fish in cooler water during spring, which might have been related to body size dependent competitive interactions. The trend was reversed in summer, with larger fish in warmer water, perhaps due to the availability of preferred prey (e.g. squid) and directional swimming behavior characteristic of sockeye spawning migration. Assuming salmon are growth-optimizers in this environment, my results suggest that winter resi- dency for sub-adults is restricted to north of latitude 54° N. Furthermore, peaks in feeding and growth shifted from a central position in the gulf during spring toward the southeast during summer, with an attendant increase in forage quality. I hypothesize that these patterns are likely to be important in drawing maturing British Columbia salmon toward their natal rivers and providing the energy needed to fuel their costly river migration during mid-summer.
Correlated Fracture Network Modeling Using Simulated Annealing

Knowledge of the orientation and spatial distribution of fractures in rocks is important for predicting the flow of fluids. Masihi et al. (2007) developed a new method of modeling these distributions beginning with theoretical results from the physics of fracturing. We implemented and extended this modeling technique to generate models that better incorporate field observations. The method starts with an energy function based on the pair-wise spatial correlation of fractures that also serves as an objective function for a simulated annealing algorithm (SA) that generates realizations of correlated fracture networks. We improved this technique by incorporating periodic boundary conditions, including criteria to limit maximum range of the pair-wise calculations, and by suggesting methods to constrain models to match field data. For most subsurface rocks (with Poisson ratio ν = 0.25), this method generates orthogonal sets of fractures, a pattern that is commonly observed during basin formation or subsidence. This new method is compared with conventional discrete fracture network (DFN) modeling by computing the fractal dimension of the networks. We also examine the implications for seismic reservoir characterization by computing effective seismic velocities and the resulting synthetic seismograms. The new approach can be considered better than DFN as DFN generates realizations based on only statistical distributions, without any knowledge of physics of fracturing.
MR Imaging of the Pancreas: 1.5T versus 3T

Pancreatic cancer has an almost uniformly grim prognosis. Early detection has the potential to improve survival, however. One promising approach to increase detection rates is the use of MR imaging at 3T. Imaging at 3T improves temporal or spatial resolution for pancreatic evaluation. Known challenges of imaging at 3T, such as increased power deposition and B1 field inhomogeneity, are not significant limitations for pancreatic imaging. Preliminary results suggest that the signal-to-noise ratio can be as much as twice as high as at 1.5T, particularly after contrast administration. Evaluation of the hepatobiliary ducts is comparable or superior to that at 1.5T. Additional studies are needed to determine if the improved image quality translates into improved sensitivity for disease.
My Hidden VA List

A VA physician's personal list of patients, alive and dead, is a treasure trove of history from World War II to Afghanistan. It reflects a system that, for all its woes, remains a singular presence in the confused patchwork of medical care that is American medicine.
Spectral analysis for electroencephalograms: mathematical determination of neurophysiological relationships from records of limited duration.

Spectral analysis is a mathematical method which contains and generalizes frequency analysis. The form of spectral analysis most applicable to EEG is tutorially presented, using both algebraic formulae and four simplified illustrative examples. The examples are each converted into an autocorrelogram and auto-spectrogram, functions whose graphic presentation clarifies the structure of each example, partly by emphasizing regular at the expense of irregular components, partly by analyzing the intensity of regular activity into components at each frequency. Then the formulae for cross-correlograms and cross-spectrograms are presented, and illustrated by converting pairs of examples into functions which clarify their interrelationships. Not only are the advantages of autospectrograms retained by cross-spectrograms, but they also emphasize activity shared between two traces, and include the mean phase angle relating such shared activity, at each frequency. The coherence function and transfer function, calculated next, are the analogs of correlation coefficient and regression coefficient. The coherence function is applied not only to calculate the “quantity of interdependence” between pairs of illustrative examples, but also to supply probable bounds on the other calculated relationships. Finally, discussion of the assumptions underlying spectral analysis prepares the method for application to actual EEG, given in preceding papers.
Geometric methods for the study of local stability

Abstract A classical result by Hartman shows that near a hyperbolic equilibrium a system is (strongly) locally conjugate to its linearization. This result can be read “backwards”: near the equilibrium, a linear hyperbolic system is locally conjugate to its perturbations of order higher than one. We show a geometric method that allows us to extend this result to quasi-hyperbolic equilibria, provided the perturbation is of sufficiently high order. The proof of the main result uses Lewowicz’s method of Lyapunov functions of two variables.
Bovine natural cell mediated cytotoxicity (NCMC): activation by cytokines.

Abstract Incubation of bovine peripheral blood mononuclear leukocytes (PBML) with the cytokines (CK) IL-2, α-IFN, γ-IFN or IL-4 resulted in significant increases in natural cell mediated cytotoxicity (NCMC) over endogenous levels, as determined in an 18 h 51Cr-release assay using the human K562 or mouse Yac-1 target cell lines. Endogenous cytotoxic activity of bovine natural effector cells (NEC) using K562 or Yac-1 target cells was minimal (killing