cssi/SciSciGPT-SciSciNet huggingface dataset:
Risk of antibiotic treatment failure in premenopausal women with uncomplicated urinary tract infection.

Purpose Acute uncomplicated urinary tract infections (UTIs) are among the most common indications for antibiotic prescriptions in otherwise healthy women. We compared the risk of treatment failure of antibiotic regimens for outpatient treatment of UTI in real-world practice. Methods We identified non-pregnant, premenopausal women diagnosed with uncomplicated, lower tract UTI and prescribed an oral antibiotic with activity against common uropathogens. We used propensity score-weighted Kaplan-Meier functions to estimate 30-day risks and risk differences (RD) for pyelonephritis and UTI-related antibiotic prescription switch. Results Of 1 140 602 patients, the distribution of index prescriptions was 44% fluoroquinolones (non-first-line), 28% trimethoprim-sulfamethoxazole (TMP/SMX) (first-line), 24% nitrofurantoin (first-line), 3% narrow-spectrum β-lactams (non-first-line), 1% broad-spectrum β-lactams (non-first-line), and 1% amoxicillin/ampicillin (non-recommended). Compared to the risk of pyelonephritis for nitrofurantoin (0.3%), risks were higher for TMP/SMX (RD, 0.2%; 95% CI, 0.2%-0.2%) and broad-spectrum β-lactams (RD, 0.2%; 95% CI, 0.1%-0.4%). Compared to the risk of prescription switch for nitrofurantoin (12.7%), the risk was higher for TMP/SMX (RD 1.6%; 95% CI 1.3%-1.7%) but similar for broad-spectrum β-lactams (RD -0.7%; 95% CI -1.4%-0.1%) and narrow-spectrum β-lactams (RD -0.3%; 95% CI -0.8% - 0.2%). Subgroup analyses suggest TMP/SMX treatment failure may be due in part to increasing uropathogen resistance over time. Conclusions The risk of treatment failure differed by antibiotic agent, with higher risk associated with TMP/SMX versus nitrofurantoin, and lower or similar risk associated with broad- versus narrow-spectrum β-lactams. Given serious safety warnings for fluoroquinolones, these results suggest that nitrofurantoin may be preferable as the first-line agent for outpatient treatment of uncomplicated UTI. This article is protected by copyright. All rights reserved.
Multi-Relational Data Characterization by Tensors: Tensor Inversion

Recent research attention has been paid to solve tensor equations. Existing solutions to tensor equations are mostly based on the iterative approach due to lack of sufficient theoretical framework governing how to find the inverse of an arbitrary tensor. In this work, we aim to establish a new theoretical framework missing from the literature so that a new algorithm is devised to determine the exact inverse of an arbitrary tensor, which is beyond the capability of the current iterative algorithms. We present theorems to derive the general formula of both inverse and pseudo inverse of an arbitrary tensor so that the inverse of an arbitrary tensor can be constructed from the tensor itself and its partial inverse. A new tensor inversion algorithm is introduced to carry out the exact inverse or the Moore-Penrose inverse should it not be invertible. The main contribution of our proposed approach is that we can always solve any tensor equation while additional restrictions have to be imposed for the existing iterative algorithms to converge on the other hand. The memory- and computational-complexities of our proposed new approach and existing iterative algorithms are also analyzed and compared.
AIM2 inflammasome activation in astrocytes occurs during the late phase of EAE

Inflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory responses through their effector cytokines, IL-1β and IL-18. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are such autoimmune conditions influenced by inflammasomes. Despite work investigating inflammasomes during EAE, little remains known concerning the role of inflammasomes in the central nervous system (CNS) during the disease. Here we use multiple genetically modified mouse models to monitor activated inflammasomes in situ based on ASC oligomerization in the spinal cord. Using inflammasome reporter mice, we found heightened inflammasome activation in astrocytes after the disease peak. In contrast, microglia and CNS-infiltrated myeloid cells had few activated inflammasomes in the CNS during EAE. Astrocyte inflammasome activation was dependent on AIM2, but low IL-1β expression and no significant signs of cell death were found in astrocytes during EAE. Thus, the AIM2 inflammasome activation in astrocytes may have a distinct role from traditional inflammasome-mediated inflammation.
The MIT Bag Model: The Dirac Equation for a Quark Confined to a Spherical Region

Quarks, like the leptons (electrons, μ and τ mesons) are Dirac s = 1/2 particles. Unlike the leptons, quarks have additional internal degrees of freedom, specified by “flavor” (including isospin that determines their charge) and “color,” They come in three colors and three generations of isospin doublets (u, d; up and down quarks; s, c; strange and charmed quarks; and b, t; bottom and top quarks). They appear in nature only in “colorless” combinations corresponding to the scalar irreducible representations of the color symmetry SU(3) [the analogue of S = 0 multiparticle spin states, corresponding to the scalar irreducible representations of SU(2)]. The “colorless” combinations can arise either from quark—antiquark combinations or combinations of three quarks. Protons, e.g., are made of two up quarks, each with charge of + 2/3e, and one down quark with charge − 1/3e, whereas neutrons are made of one up quark and two down quarks, total charge = (+2/3 − 1/3 − 1/3)e = 0. These three-quark systems have a total spin, S = 1/2, and isospin, I = 1/2, with M 1 = ±1/2. The quark aggregates are confined to finite regions of space, for the three-quark aggregates of the nucleon, to a region of approximately 1.2 fm. The confinement mechanism is not at all understood. One of the most successful phenomenological models for quark confinement is the “MIT bag model,” named after the institution of the inventors of the model. In this model, it is simply assumed the quarks are confined to a spherical region of space, with a radius, r = a, and V(r) = 0 for r a. Our discussion of the Klein paradox, however, should convince us an infinite potential is unable to confine a relativistic particle. It may be enough to solve a model in which the quark is in free particle motion inside the region for r < a, but is subject to boundary conditions at r = a that simply dictate the confinement.
Stem cell origin and microenvironment contribution for NF1-associated neurofibromas

The tumor predisposition disorder Neurofibromatosis type I (NF1) is one of the most common genetic disorders of the nervous system. It is caused by mutation in the Nf1 tumor suppressor gene, which encodes a GTPase Activating Protein (GAP) that negatively regulates p21-RAS. The development of malignant nerve tumors and neurofibromas, the most frequent tumors in NF1, is a serious complication of the disease. However, little is known about the molecular mechanisms mediating the initiation and progression of these complex tumors, as well as the identity of the specific cell type that gives rise to dermal or cutaneous neurofibromas. In this study, we identify a population of neural crest related stem cells residing in the dermis termed Skin Derived Precursors (SKPs) that, through loss of Nf1, form neurofibromas. We propose that SKPs, or their derivatives, are the cell of origin of dermal neurofibroma. We also provide evidence that additional signals from the non-neoplastic cells in the tumor microenvironment play essential roles in neurofibroma tumorigenesis. These new findings provide a novel approach to gain a greater understanding of the molecular pathogenesis of neurofibroma and exploit innovative therapeutic approach in clinical trial to treat NF1-associated neurofibromas.
Phase Space Portraits of an Unresolved Gravitational Maxwell Demon

In 1885, during initial discussions of J. C. Maxwell's celebrated thermodynamic demon, Whiting (1) observed that the demon-like velocity selection of molecules can occur in a gravitationally bound gas. Recently, a gravitational Maxwell demon has been proposed which makes use of this observation [D. P. Sheehan, J. Glick, and J. D. Means, Found. Phys. 30, 1227 (2000)]. Here we report on numerical simulations that detail its microscopic phase space structure. Results verify the previously hypothesized mechanism of its paradoxical behavior. This system appears to be the only example of a fully classical mechanical Maxwell demon that has not been resolved in favor of the second law of thermodynamics.
Function of the hypoxic myocardium. Experimental and clinical aspects.

A fundamental characteristic of cardiac muscle function is rapid deterioration consequent to interruption of myocardial blood supply and oxygen delivery. Experimental and clinical studies have demonstrated, in association with myocardial ischemia or hypoxia, derangements of cardiac mechanical and pump performance, metabolic processes, electrical activity and structure. Deprivation of oxygen is the major factor producing these alterations, but reduced substrate delivery and accumulation of the products of cell metabolism and breakdown are contributing factors. After the onset of myocardial ischemia, there is a period during which the ensuing functional and subcellular structural alterations are reversible with restoration of oxygen supply. After this interval, structural damage is irreversible and there is permanent loss of myocardium. The degree of functional impairment is most closely related to the quantity of myocardium involved. In patients with stable coronary artery disease, clinical cardiac failure is not usually evident in the absence of previous loss of left ventricular myocardium, as occurs with infarction. However, evidence of transient, reversible impairment of ventricular muscle and pump performance is present during episodes of angina pectoris. Myocardial infarction or, less frequently ischemia, is associated with permanent elimination of normal contractile performance in a localized area of myocardium (asynergy). Evidence of cardiac failure is apparent when 20 to 25 percent of left ventricular muscle is asynergic. The standard electrocardiogram is useful in estimating location and degree of asynergy and also cardiac pump performance by the presence and location of pathologic Q waves and associated electrocardiographic abnormalities. In acute myocardial infarction, the shock syndrome is associated with loss of 40 percent or more of left ventricular myocardium. Since in-hospital prognosis in acute myocardial infarction is closely related to extent of left ventricular damage, estimation of the latter would be helpful in applying the most appropriate forms of therapy in these patients. Recent innovations utilizing serum enzyme analysis and isotopic imaging of left ventricular myocardium have provided promising, noninvasive means of achieving this goal.
Characterization of a Blood Group B Glycolipid, Accumulating in the Pancreas of a Patient with Fabry's Disease

Abstract An accumulation of a ceramide hexasaccharide was found in the pancreas of a patient with Fabry's disease, in addition to the accumulation of ceramide trihexoside and ceramide digalactoside. The ceramide hexasaccharide was isolated and identified as a blood group B-active glycolipid with the following structure: [see PDF for equation] The proportion of two structures, one containing Gall → 3GlcNAc and one containing Gall → 4GlcNAc, is 4:1.
Remote functionalization and molecular modeling: Observations relevant to the barton and hypoiodite reactions

Abstract Calculated distances in computationally minimized substrate structures correlate with experimental results, offering a predictive basis for the Barton reaction and related processes.
When Patents Threaten Science

Patents should not be used to protect laws of nature, products of nature, or mathematical formulas.
Evaluation and Enhancements for NORMA: Student User Suggestions

In an advanced database design class, students used NORMA for the first time to do several data modeling assignments. One of the graded requirements was to write a comprehensive feedback memo directed primarily to the developers of the data modeling tool. The memo was to be broken down into good points, bad points, problems, and suggestions for improvement or enhancement. This provides a unique opportunity to gather substantial feedback from users, since the students are highly motivated to use the tool to complete each assignment, working through any problems or frustrations they faced. Giving up was not an option. This paper provides a summary report of the experiences and suggestions as captured in the feedback memos. Several suggestions would be relevant for other fact-oriented design tools. Overall, students really liked using the tool, finding it to be reasonably intuitive and easy to use. Data model verbalization was the most frequently mentioned benefit. The major problems related to a lack of good documentation, the convoluted and difficult process of generating a database (DDL script), and the lack of adequate data model abstraction mechanisms.
Dental X-rays and the risk of intracranial meningioma: a population-based case-control study.

BACKGROUND Ionizing radiation is a likely cause of intracranial meningioma. The authors determined whether the risk of intracranial meningioma was associated with past dental X-rays—specifically, posterior bitewings, full-mouth series, and lateral cephalometric and panoramic radiographs. METHODS The authors conducted a population-based case–control study of residents of King, Pierce, and Snohomish counties in western Washington State. Case patients (n = 200) had an incident intracranial meningioma that was confirmed histologically during life between January 1995 and June 1998. The authors used random-digit dialing and Medicare eligibility lists to identify two control subjects to be matched to each case patient based on age and gender. Exposures were determined during an in-person interview. The authors compared self-report and dental records in a subset of study participants. RESULTS Of the 4 dental X-ray procedures evaluated, only the full-mouth series (specifically, ≥ 6 over a lifetime) was associated with a significantly increased risk of meningioma (odds ratio, 2.06; 95% confidence limits, 1.03–4.17). However, evidence for a dose-response relation was lacking (P for trend = 0.33). The risk was elevated with the aggregate number of full-mouth series in 10-year periods from approximately 15–40 years before diagnosis, with significant elevations in the 10-year periods beginning 22–30 years before diagnosis. The risks in these analyses were even greater when only women were considered. CONCLUSIONS Dental X-rays involving full-mouth series performed 15–40 years ago, when radiation exposure from full-mouth series was much greater than it is now, were associated with an increased risk of meningioma. The authors did not observe an increased risk with bitewings, lateral cephalometric, and panoramic radiographs. Cancer 2004;100:1026–34. © 2004 American Cancer Society.
The role and treatment of irresponsibility in dysfunctional relationships

This article explores the role of personal responsibility in dysfunctional relations. The premise is that the stances one or both partners take with regard to their relationship responsibilities predict the success or failure of that relationship. The four parts of this article include a definition of responsibility, a delineation of four crucial areas of relationship responsibility, a listing of irrational beliefs that block responsibility, and an outline of irresponsibility treatment.
Thermodynamics of the Various High Temperature Transformations of Kaolinite

Thermodynamic calculations of ΔG for all possible transformations of metakaolin at the temperature of the first DTA exothermic peak indicates that the most stable transformation is the one that yields mullite rather than γ-alumina. The energy of crystallization of γ-alumina is quite small—36,513 cal per mol, compared with the energy of crystallization of mullite—336,180 cal per mol. Furthermore, the crystallization of γ-alumina is very slow, and the crystal growth never produces crystallite sizes much larger than the lower end of the colloidal region. Hence, the gradual release of the small amounts of energy liberated during the crystallization of γ-alumina would be extremely difficult to detect by DTA methods.
Antisense peptide nucleic acids conjugated to somatostatin analogs and targeted at the n-myc oncogene display enhanced cytotoxity to human neuroblastoma IMR32 cells expressing somatostatin receptors

Peptide nucleic acid (PNA) sequences are synthetic versions of naturally occurring oligonucleotides which display improved binding properties to DNA and RNA, but are still poorly internalized across cell membranes. In an effort to employ the rapid binding/internalization properties of somatostatin agonist analogs and the over-expression of somatostatin receptors on many types of tumor cells, PNAs complementary to target sites throughout 5'-UTR, translation start site and coding region of the n-myc oncogene were conjugated to a somatostatin analog (SSA) with retention of high somatostatin biological potency. IMR32 cells, which over-express somatostatin receptor type 2 (SSTR2) and contain the n-myc oncogene, were treated with these PNA-SSA conjugates. The results show that PNA conjugates targeted to the 5'-UTR terminus and to regions at or close to the translation start site could effectively inhibit n-myc gene expression and cell growth, whereas the non-conjugate PNAs were without effect at similar doses. The most potent inhibition of cell growth was achieved with PNAs binding to the translation start site, but those complementary to the middle coding region or middle upstream site between 5'-UTR and translation start site displayed no inhibition of gene expression. These observations were extended to four other cell lines: GH3 cells which express SSTRs with the n-myc gene, SKNSH cells containing a silent n-myc gene without SSTR2, HT-29 cells carrying the c-myc but no n-myc gene, and CHO-K1 cells lacking SSTR2 with n-myc gene. The results show that there was almost no effect on these four cell lines. Our study indicates that PNAs conjugated to SSA exhibited improved inhibition of gene expression possibly due to facilitated cellular uptake of the PNAs. These conjugates were mRNA sequence- and SSTR2-specific suggesting that many other genes associated with tumor growth could be targeted using this approach and that SSA could be a novel and effective transportation vector for the PNA antisense strategy.
Application of cryopreservation techniques to islet cell allotransplantation.

Abstract This study continues our investigations in the area of canine islet cell cryopreservation. Islet cell allografts were frozen using a simple method to −196 °C with rapid freezing rates and dimethyl sulfoxide as the cryoprotectant. Good in vitro viability was observed using trypan blue dye exclusion. After intrasplenic transplantation, grafts which did not reject were able to maintain normoglycemia for periods of greater than 60 days. The use of either Cy A as an immunosuppressant or ALG as a graft pretreatment contributed to prolongation of allograft survival in these long-term surviving recipients. These results encourage further studies in this area for potential future clinical application of this technique to human pancreas.
Discordance between intramuscular triglyceride and insulin sensitivity in skeletal muscle of Zucker diabetic rats after treatment with fenofibrate and rosiglitazone.

Aim: Intramyocellular triglyceride (IMTG) correlates with insulin resistance, but there is no clear causal relationship. Insulin resistance and associated hyperinsulinaemia may increase IMTG, via the insulin-regulated transcription factor, sterol regulatory element–binding protein 1 (SREBP-1). PPAR agonists may also affect IMTG via changes in insulin sensitivity, SREBP-1 or other factors. Methods: We examined skeletal muscle IMTG and SREBP-1 expression, and metabolic parameters in Zucker diabetic fatty rats (ZDF) after 25 weeks of PPAR-γ or PPAR-α administration. Results: Compared with Zucker lean rats (ZL), untreated ZDF had significantly higher weights, serum glucose, insulin, free fatty acids, total cholesterol and triglycerides. IMTG and SREBP-1c messenger RNA (mRNA) were also higher in untreated ZDF; both were decreased by fenofibrate (FF). Rosiglitazone (Rosi), despite marked improvement in glycaemia, hyperinsulinaemia and hyperlipidaemia, failed to affect SREBP-1 expression, and increased body weight and IMTG. Rosi/FF combination caused less weight gain and no IMTG increase, despite metabolic effects similar to Rosi alone. Conclusions: IMTG and SREBP-1c mRNA are high in the ZDF. FF and Rosi both improved insulin sensitivity but had opposite effects on IMTG. Thus, there was a clear discordance between insulin sensitivity and IMTG with PPAR agonists, indicating that IMTG and insulin sensitivity do not share a simple relationship.
A.C.-INDUCED D.C.MAGNETIZATION OF A FERROMAGNETIC AMORPHOUS ALLOY BELOW THE CRITICAL FIELD

Abstract The ferromagnetic amorphous alloy Fe 78 B 13 Si 9 (Allied 2605 S2) can be magnetized below the critical magnetic field of about 0.025 Oe by superposing a suitable a.c. magnetic field such as 0.05 Oe at 100 Hz. With this additional a.c. field, the d.c. magnetic induction is 5.6 kG in a d.c. field of 0.02 Oe as opposed to 60 G without the a.c. field.
Ultraviolet light emitting diodes by ammonia molecular beam epitaxy on metamorphic (202¯1) AlGaN/GaN buffer layers

Abstract In this paper we demonstrate ultraviolet (UV) light emitting diodes (LEDs) grown on metamorphic AlGaN buffers on freestanding GaN ( 20 2 ¯ 1 ) substrates by ammonia assisted molecular beam epitaxy (MBE). Misfit and related threading dislocations were confined to the stress relaxed, compositionally graded buffer layers, and single quantum well devices emitting at 355, 310 and 274 nm were grown on top of the graded buffers. The devices showed excellent structural and electrical (I–V) characteristics.
Pathophysiology of tachycardia- and bradycardia-dependent block in the canine proximal his-purkinje system after acute myocardial ischemia

Abstract An experimental model for the study of conduction disturbances in the proximal His-Purkinje system after acute myocardial ischemia was produced in 24 dogs by ligation of the anterior septal artery. Eighteen of the 19 dogs that survived the initial vulnerable arrhythmic period showed different degrees of conduction disturbance in the bundle of His, right and left bundles or any combination thereof usually within 1 to 2 1 2 hours after ligation. In 14 experiments normal conduction was restored within 8 hours. In all cases with bundle branch block, the block was initially demonstrated on increasing or slowing the heart rate, with a range of intermediate rates at which conduction was normal. Within 45 minutes the block became constant at all heart rates, but within 2 to 6 hours was again replaced by normal conduction at Intermediate rates and, finally, consistent normal conduction. In 12 experiments showing intra-His bundle block (always demonstrated by splitting of the His potential into two deflections, Hb1 and Hb2) increasing the rate resulted in second or third degree block with the blocked impulse localized between the two deflections. In 5 of 12 experiments, slowing the rate gave rise to first degree intra-His bundle block (lengthening of the Hb1-Hb2 interval). Our in vitro observations suggested that the initial phase of tachycardia- and bradycardia-dependent block in the proximal His-Purkinje system can be explained by characteristic changes in the electrophysiologic properties of two groups of Purkinje fibers which may be due to differential localization of metabolites released in the ischemic zone. Tachycardia-dependent block was based on a time-dependent response of Purkinje fibers partially depolarized by an increase in extracellular concentration of potassium ion. Bradycardia-dependent block was explained by a slight to moderate decrease of resting potential, a normal slope of phase-4 depolarization and reduced membrane responsiveness associated with shift of the threshold potential toward zero. Contrary to previous data, our findings indicate no relation between enhanced automatlcity of pacemaker cells and bradycardia-dependent conduction disturbances.
Indomethacin inhibits the uptake of 22sodium by ovine trophoblastic tissue in vitro.

Blastocysts from several species synthesize prostaglandins in vitro, but the exact functions of the prostaglandins are unknown. The purpose of this study was to determine if indomethacin, an inhibitor of prostaglandin synthesis, would inhibit the uptake of 22sodium ([22Na]) by ovine trophoblastic tissue. To determine the concentration of indomethacin that would inhibit the synthesis of PGF2α and 13,14-dihydro-15-keto-PGF2α (PGFM) by blastocysts, blastocysts were collected from ewes 16 days after mating, sliced into pieces approximately 2 mm in length and incubated for 48 h at 37°C in 2 ml of medium containing either 0, 0.2, 0.4, 0.8 or 1.6 mM of indomethacin. Concentrations of indomethacin >0.2 mM reduced (P<.01) trophoblastic release (ng/μg DNA) of PGF2α from 205 ± 71.2 to <3.3 ± 0.2, reduced PGFM from 0.7 ± 0.1 to <0.17 ± 0.01, and inhibited formation of trophoblastic vesicles. In a second experiment, blastocysts were recovered from ewes 16 days after mating and pieces of trophoblast were incubated with [22Na] and either 0 or 0.4 mM of indomethacin. Indomethacin reduced the uptake of [22Na], which is an indirect measure of the transport of water across epithelia, from 3680 ± 1118 to 934 ± 248 cpm/μg DNA (P<.03) and prevented formation of trophoblastic vesicles. Prostaglandins produced by ovine blastocysts might be involved in controlling uptake of water, which is essential for expansion of blastocysts.
Reduction of a channel-based model for a stomatogastric ganglion LP neuron

Buchholtz et al. constructed a detailed conductance-based model of the LP cell of the stomatogastric ganglion of crustacea based upon the experimental work of Golowasch. Their model incorporated seven ionic currents and had 13 dynamical variables. We have produced a simplification of this model that has a seven-dimensional phase space by using the method of equivalent potentials, suggested by Abbott and Kepler, to combine several dynamical variables with similar time scales. Analysis of the dynamics of the reference and reduced model reveals similar bifurcation diagrams and similar dynamical behavior of the individual ionic currents.
Thyrotropin- and prostaglandin E2-responsive adenyl cyclase in thyroid plasma membranes.

Abstract We studied TSH and PGE 2 effects on adenyl cyclase in bovine thyroid plasma membranes. With [α- 32 P]ATP as substrate, there was no PGE 2 effect on adenyl cyclase in plasma membranes highly responsive to TSH and NaF (7- to 12-fold and 12- to 15-fold increase over control, respectively). Since enhanced plasma membrane Na + -K + -activated ATPase activity (40-fold greater than original homogenate) might have resulted in significant ATP hydrolysis despite the presence of an ATP-regenerating system, we repeated these studies with 32 P-labeled 5′-adenylyl-imidodiphosphate ([ 32 P]AMP-PNP), an ATP analogue which is an ATPase-resistant substrate for adenyl cyclase. With AMP-PNP as substrate, adenyl cyclase in all plasma membranes tested showed a dose-related response (133% to 226% increase) to both TSH (5 to 250 mU/ml) and PGE 2 (10 −6 to 10 −4 M), which response was inhibited, in each instance, by the prostaglandin antagonist 7-oxa-13-prostynoic acid (PY 1 , 10 −5 M). Since guanyl nucleotides, e.g. GTP, have been shown to enhance basal and hormone-stimulated adenyl cyclase in liver plasma membrane, we examined the effect of 0.1 mM GTP on thyroid plasma membrane adenyl cyclase using [α- 32 P]ATP as substrate. In the presence of GTP, both basal and TSH-stimulated adenyl cyclase were enhanced two fold; in addition, a stimulatory PGE 2 effect (two-fold increase) was reproducibly demonstrated. In contrast, the effect of fluoride ion was inhibited by GTP. PY 1 inhibited the stimulatory effects of both TSH and PGE 2 under these conditions. These findings suggest great similarity between TSH and PGE 2 adenyl cyclase receptor(s) in thyroid and are consistent with the premise that prostaglandins play an important role in TSH stimulation of thyroid function.
The Pursuit Of Excellence: Michael E. Debakey As Mentor, Colleague, And Friend

This past April, renowned heart surgeon Michael E. DeBakey journeyed to the nation’s capitol, where he was awarded the Congressional Gold Medal by President George W, Bush. Inscribed on the medal is a quote of Dr. DeBakey’s that reads, "The pursuit of excellence has been my objective in life." For more than three decades, Michael DeBakey has been mentor, colleague, and friend to fellow MDHVC surgeon Gerald Lawrie. In an interview with William L. Winters Jr., cardiologist and editor-in-chief of the Journal of the Methodist DeBakey Heart & Vascular Center, Dr. Lawrie shares his experiences pursuing excellence alongside one of medicine’s greatest pioneers.
An Investigation of The Effects of Temperature on Fatigue Crack Growth Behavior of a Cast Nearly Lamellar Ti-47A1–2Cr-2Mn + 0.8 Vol. %TiB 2 Gamma Titanium Alloy

This paper presents the results of a study of the effects of temperature on fatigue crack growth in Ti-47Al-2Cr-2Mn + 0.8 Vol. %TiB2 gamma titanium aluminide intermetallics. Fatigue crack growth rate data are presented for the cast lamellar microstructure at 25,450 and 750°C. The trends in the fatigue crack growth rate data are explained by considering the combined effects of crack-tip deformation mechanisms and oxide-induced crack closure. Faster fatigue crack growth rates at 450°C are attributed to the high incidence of irreversible deformation-induced twinning, while slower crack growth rates at 700°C are due to increased deformation by slip and the effects of crack-tip shielding provided by oxide-induced wedging, which is analyzed using a modified Dugdale-Barenblatt model.
Structural basis for developmentally regulated changes in cadherin function at synapses

Members of the cadherin family of calcium-dependent cell adhesion molecules can bind homophilically across central nervous system (CNS) synapses, but experimental evidence indicates the nature of their contribution to synapse structure and function changes over time. We asked whether changes in function correspond to differences in intrasynaptic distribution. Using quantitative immuno-electronmicroscopy, we determined where cadherins are localized within synapses at key developmental stages in cultured hippocampal neurons and in hippocampus in vivo. At 5–6 days in culture, when most synapses are newly formed, cadherins are regularly and evenly distributed at synaptic clefts throughout the active zone. In contrast, at 14 days, when the majority of synapses are comparatively mature, cadherin labeling concentrates in discrete clusters. Such clusters can occur at any place within or immediately surrounding synaptic clefts. To assess whether this change in distribution is unique to neurons grown in culture, we compared the distribution of cadherins in the CA1 region of hippocampus at postnatal days 2, 3 (P2–3) and in adult. Consistent with our observations in cultured neurons, synapses in P2–3 hippocampus most often exhibit cadherins distributed regularly throughout the cleft, while adult synapses show predominantly discrete concentrations at single sites. The early developmental pattern of cadherin distribution can also be detected at occasional synapses in adult tissue. Such synapses also have morphological features consistent with immature synapses, suggesting that intrasynaptic cadherin distribution is a feature that may distinguish synapse age. J. Comp. Neurol. 495:324–335, 2006. © 2006 Wiley-Liss, Inc.
Radioautographic and chemical evidence for [5-3H]mevalonate incorporation into cholesterol by rat villous absorptive cells

Abstract The cellular sites of mevalonic acid incorporation into cholesterol in the small intestinal wall were studied by radioautographic and chemical methods. [5- 3 H]Mevalonate was instilled into the serosal compartment of rat ileal everted sacs and incubated for 60 min. Portions of the sacs were fixed in digitonin-containing aldehyde, digitonin-free aldehyde or used directly for chemical analyses. Radioautographs of 1 μm Epon-embedded sections from digitonin-aldehyde fixed tissue showed heavy labeling of absorptive cells lining the upper two-thirds of the villi, moderate labeling of those lining the lower third and little labeling of crypt epithelium. Within absorptive cells, grain density over the microvillous region was higher than that over the rest of the cytoplasm. After fixation and acetone dehydration, 24.9% of lipid radioactivity was retained in tissue. Thin-layer chromatography revealed that 85.1% of retained lipid radioactivity was in unesterified sterols. This represented 71.4% of the newly synthesized 3 H-labeled unesterified sterols found in companion unfixed segments of the sacs. In contrast, digitonin-free aldehyde fixation resulted in only light labeling of radioautographs of absorptive cells and in only 6.6% retention of 3 H-labeled unesterified sterols. These findings indicate that exogenously administered 3 H-labeled mevalonate is incorporated into digitonin-precipitable sterols primarily in villous absorptive cells in everted sacs of rat ileum.
Development and Characterization of a Surgical Mouse Model of Reflux Esophagitis and Barrett's Esophagus

Ideally, an animal model of Barrett's esophagus should recapitulate the human disease histologically and immunohistochemically, and be readily susceptible to genetic manipulation. We have developed such a model using a strain of mice commonly used for transgenic and knockout manipulations. We induced reflux by esophagojejunostomy (EJ) in 20 C57Bl/6 mice. At defined time points, sections of the esophagus were stained with H&E and Alcian blue, and immunohistochemical staining was performed for Sox9 (a transcription factor in Barrett's metaplasia), cytokeratin (CK) 8/18 (a columnar marker) and CK14 (a squamous marker). Procedural mortality was 40% for the first ten animals, 20% for the next 10. Reflux esophagitis developed by 13 weeks, and intestinal metaplasia with goblet cells developed by 34 weeks. The metaplasia expressed CK8/18, but not CK14, and exhibited nuclear immunostaining for Sox9. Nuclear Sox9 was also seen in scattered basal cells of squamous epithelium close to the EJ anastomosis. EJ can be performed successfully in C57Bl/6 mice, resulting in reflux esophagitis and intestinal metaplasia that exhibits phenotypic and molecular features of human Barrett's metaplasia. This surgical model in a mouse strain that is easy to manipulate genetically should be a valuable tool for studying the pathogenesis of Barrett's esophagus.
Jacobian matrix singularity based pareto front identification for multi-objective problems

This paper presents a new structured method to effectively determine the complete boundary, including the Pareto frontier, of a multi-objective optimization problem. The proposed technique identifies the boundary in the cost space by systematically searching the design parameter space for points which make the Jacobian matrix of the cost vector singular. This corresponds to the identifying a manifold in parameter space which results in a reduced dimensional manifold in the cost space. Since the boundary of the cost space implies a reduced dimensional manifold, a systematic approach is now available for exact identification of the boundary in the cost space. The efficacy of the proposed method is demonstrated on one optimization and one optimal control problem, in this paper.
First observations of COTR due to a microbunched beam in the VUV at 157 nm

The self-amplified spontaneous emission free-electron laser experiments at the Advanced Photon Source are now operating in the VUV at 157 nm for a user experiment. In conjunction with these runs, we have obtained the first coherent optical transition radiation data due to the microbunching of the electron beam in the VUV. We have used both near- and far-field focusing by selecting the spherical mirror with the appropriate focal length for the distance to the CCD chip. The optics are such that much higher resolution than our visible system is attained with calibration factors of 11 μm/pixel and 10 μrad/pixel, respectively. Localized effects in the distributions in both focal conditions are being addressed.
Renal and blood pressure phenotype in 18-mo-old bradykinin B2R(/) CRD mice

Aberrant gene-environment interactions are implicated in the pathogenesis of congenital renal dysgenesis (CRD), a leading cause of renal failure in infants and children. We have recently developed ...
Effects of haploidy and hybridization on the activities of four dehydrogenases in frog embryos.

Abstract Total activities of four enzymes, malate dehydrogenase, lactate dehydrogenase, isocitrate dehydrogenase, and 6-phosphogluconate dehydrogenase were measured in diploid and androgenetic haploid embryos resulting from crosses of Rana pipiens pipiens and Rana pipiens sphenocephala . Developmental curves of these enzyme activities were compared with the DNA content of the embryos. The results suggest that decreased total enzyme activity in abnormal androgenetic haploid hybrids is due to the effects of reduced cellular proliferation and cellular degradation caused by a general nucleocytoplasmic incompatibility, not to the factors directly affecting the synthesis of each enzyme.
A diterpene related to cladiellin from a pacific soft coral

Abstract A new diterpene 2 from a soft coral collected at Majuro Atoll has been related to cladiellin ( 1 .
Cross-linking surface immunoglobulin increases the stiffness of lymphocytes

Abstract Cross-linking surface immunoglobulin (sIg) on B-lymphocytes causes a substantial increase in the mechanical stiffness of the cells. This has been demonstrated using a new method for measuring cellular deformability. The method is based on a device, the “Cell Poker”, which we use to determine the force required slightly to indent or compress a cell adherent to a rigid substrate in culture. Cross-linking of sIg by bivalent anti-sIg antibodies is necessary to elicit the increase in stiffness; binding of monovalent Fab fragments is insufficient. The increase in stiffness is partially reversed by cytochalasin D and by completion of the capping of the cross-linked sIg. The modulation of cellular deformability and the induction of cellular dynamic processes such as capping are similar in their requirements for cross-linking sIg and in their sensitivity to cytochalasins. This suggests that both kinds of responses stem from similar cellular processes and structures. These results emphasize the mechanical capability of lymphocytes and suggest that the physiological functions of these cells are likely to employ this capability.
Effect of War on Crime: A Study of Sentenced Prisoners 1933 to 1986

The rates of male and female sentenced prisoners from 1933 to 1986 in the USA were associated with the military participation rate in simple correlational and multiple regression analyses.
Contribution of air medical personnel to the airway management of injured patients

Introduction: Air medical services are being pressured to demonstrate their value. Airway management is the first priority of care when treating injured patients in the prehospital setting. Injured patients with decreased Glasgow Coma Scale (GCS) are candidates for advanced airway procedures and air medical transport. Research Question: The purpose of this study was to determine the extent of air medical crews' contributions to the airway management of the injured patient in the prehospital setting. Method: A study of adult (age > 12 years) injured patients encountered in a field setting, whose GCS on the arrival of the air medical crew was ≤8, was conducted for 21 months (Feb. 1, 1991–Oct. 31, 1992). Results: During the study period, 174 patients who met the criteria were transported by the air medical crew. All but one received advanced airways including oral tracheal intubation, nasal tracheal intubation or cricothyrotomy. Of those, 68 (39%) of these procedures were completed by ground personnel (ground group), and 105 (61%) were completed by the air medical personnel (air group). The mean GCS for the ground group was 3.69 and for the air group was 4.69. The distributions were significantly different (Wilcoxon Rank Test p = 0.0002). Nineteen percent (13/68) of the patients whose airways were successfully managed by the ground personnel had a GCS of 5 to 8, as did 44% (46/105) of the air group's patients. The groups' patients were not significantly different in age or sex distribution. Conclusion: Properly trained air medical personnel positively contribute to the prehospital care of injured patients by establishing definitive airways in patients with higher GCSs.
Hepatitis C Virus Prevention, Care, and Treatment: From Policy to Practice

The prevention of hepatitis C virus (HCV) infection and associated health conditions (eg, cirrhosis and hepatocellular carcinoma) is a public health priority in the United States. Hepatitis C virus-related morbidity and mortality is increasing at a time when the advent of highly effective therapies greatly increases opportunities to prevent HCV transmission and disease. In 2010, the Institute of Medicine recommended that national action be taken to address this "underappreciated health concern for the nation." In response, in 2011, the US Department of Health and Human Services (HHS) published a viral hepatitis action plan that guides response to the viral hepatitis epidemic by providing explicit steps to be undertaken by specific HHS agencies to improve provider training and community education; expand access to testing, care, and treatment; strengthen public health surveillance; improve HCV preventive services for injection drug users; develop a hepatitis C vaccine; and prevent HCV transmission in healthcare settings. For all aspects of the action plan, infectious disease specialists and other clinicians assume a key role in efforts to reduce HCV-related morbidity and mortality. With successful collaboration of the public and private sectors, the hepatitis C epidemic can be forever silenced.
Genetics of DNA repair in bacteria

Abstract In E. coli , DNA damage or interruption of DNA replication by a variety of treatments results in the SOS response. A coordinately regulated system of genes is depressed, leading to a variety of processes which enhance DNA repair. Through this mechanism the cell can recover from potentially lethal treatments.
Surgical removal of the olfactory bulbs increases sensitivity of the reproductive system of female rats to the inhibitory effects of late afternoon melatonin injections.

In rats, anosmia induced by olfactory bulbectomy sensitizes the neuroendocrine-reproductive axis to the inhibitory effects of the pineal gland. Thus, combined blinding (which stimulates pineal antigonadotrophic activity) and anosmia cause a marked delay in the sexual maturation of female rats. The present study tested whether anosmia would also sensitize the neuroendocrine axis to the reproductive inhibitory effects of melatonin. In the present study, young female rats were rendered anosmic and maintained under light:dark cycles of 14:10; they were given melatonin injections daily (25 μg) at either 0900 hr (AM-melatonin) or at 1800 hr (PM-melatonin)—i.e., either 3 or 12 hr after lights on, respectively. The melatonin injections were begun when the rats were 23 days of age and were continued for 35 days. By comparison with AM-melatonin, PM-melatonin injections were considerably more effective in inhibiting bodily growth as well as the weights of the anterior pituitary, ovaries, and uterus of anosmic rats. Similarly, the changes in pituitary and plasma LH and PRL levels were more obvious in the PM-treated anosmic rats than in those given melatonin in the morning. Thus, anosmia does increase the sensitivity of the neuroendocrine-reproductive axis to melatonin, provided the indoleamine is administered late in the light phase of the light:dark cycle. Anosmia by itself had no influence on the daytime levels of radioimmunoassayable melatonin within the pineal gland, whereas in blinded control rats, melatonin levels were markedly augmented.
Varicella-Associated Thrombocytopenia: Autoantibodies against Platelet Surface Glycoprotein V

Varicella zoster infection in children can be complicated by acute idiopathic thrombocytopenic purpura (ITP). To determine the etiologic mechanism of this thrombocytopenia, we studied three children with clinically diagnosed varicella infection. Immunoblot analysis of these patients' anti-platelet antibodies identified a unique band at 85 kD. Characterization of this protein revealed that it was platelet surface glycoprotein V (GPV) because it was not affected by a disulfide bond reduction but was cleaved by thrombin. Bernard-Soulier syndrome (BSS) platelets deficient in GPIb-IX and GPV did not react with the sera from our varicella-infected study patients. There was no apparent cross-reactivity between anti-varicella antibody and patients' anti-GPV Ig. We report here the first cases of GPV as the target antigen in autoimmune thrombocytopenia.
An investigation into the possibility of lasing directly from an isomeric level

Abstract A conceptual realization of a γ-ray laser is described, which is based on thermal neutron pumping of long-lived Mossbauer isotopes to obtain inversion, and the simultaneous application of techniques that destroy the effect of inhomogeneous broadening, to attain resonance. Three long-lived isotopes with the required characteristics are identified. The results of a study, using the nuclear properties of these isomers and the solid state properties of the bulk materials, are presented. Threshold conditions and pumping requirements for such a device are discussed.
Oxidative iron species and ocean challenges: a perspective.

The idea of using oxidative iron (Fe6+) to manage fouling and potentially invasive and pathogenic species in ballast water has merit and is attractive when viewed in the broadest context. Ferrate (Fe6+) has potential in ballast water management because it reduces a complex global problem to a single issue, viz.how to dispose of the waste which is predominantly Fe3+. Waste iron disposal must be considered carefully because iron limits photosynthesis in oligotropthic oceans, alters physiological processes in bacteria and animals, produces reactive oxygen species, causes nitrosative stress and increased availability enhances the virulence of pathogenic bacteria. The case is made that the oxidative iron waste should be recycled rather than discharged into the ocean.
Rapid diffusion of magic-size islands by combined glide and vacancy mechanism.

Using molecular dynamics, nudged elastic band, and embedded atom methods, we show that certain 2D Ag islands undergo extremely rapid one-dimensional diffusion on Cu(001) surfaces. Indeed, below 300 K, hopping rates for ``magic-size'' islands are orders of magnitude faster than hopping rates for single Ag adatoms. This rapid diffusion requires both the $c(10\ifmmode\times\else\texttimes\fi{}2)$ hexagonally packed superstructure typical of Ag on Cu(001) and appropriate ``magic sizes'' for the islands. The novel highly cooperative diffusion mechanism presented here couples vacancy diffusion with simultaneous core glide.