cssi/SciSciGPT-SciSciNet huggingface dataset:
Current concepts of the diagnosis of adult growth hormone deficiency

In adults, growth hormone (GH) deficiency is associated with increased visceral adiposity, decreased lean body mass, bone mineral density and exercise capacity, dyslipidemia, insulin resistance, increased cardiometabolic and fracture risk, and impaired quality of life. The aim of the present article is to review the diagnosis of GH deficiency in adults. To avoid overdiagnosis of GH deficiency, it is critical to evaluate only patients at risk for pituitary dysfunction, including those who have had sellar masses, pituitary surgery, radiation therapy, traumatic brain injury, subarachnoid hemorrhage or childhood onset GH deficiency. Evaluation for GH deficiency should be undertaken after testing and replacement of other pituitary hormone deficits. Since GH secretion is pulsatile, measuring serum GH levels randomly is not helpful in establishing the diagnosis of GH deficiency. Serum insulin-like growth factor I (IGF-I) levels lack substantial diurnal variation but also lack sufficient sensitivity and specificity in the diagnosis of GH deficiency in adults. However, adults with multiple (≥3) additional pituitary hormone deficiencies, risk factors for hypopituitarism and low serum IGF-I levels are very likely to be GH deficient. In most cases, the diagnosis of GH deficiency requires stimulation testing. These tests involve the administration of a pharmacologic agent that normally stimulates GH release from pituitary somatotrophs, including insulin, glucagon, growth hormone releasing hormone-arginine or macimorelin, followed by sampling of serum specimens at regular intervals for GH assay. Patients with a peak GH level that is below a predetermined cutpoint are classified as GH deficient. A systematic approach to the diagnosis of GH deficiency is essential in order to accurately identify adults who may benefit from GH replacement.
Mobile phone-based messaging for tobacco cessation in low and middle-income countries: a systematic review

Abstract Introduction Mobile phone-based tobacco cessation (mCessation) interventions are effective in high-income countries but their effectiveness in low and middle-income countries (LMICs) is unclear. We aimed to assess the evidence-base for mCessation interventions in LMICs by synthesizing study characteristics and to describe intervention characteristics and content. Methods Studies were included in this review if they evaluated an intervention that targeted tobacco users, were conducted in an LMIC, measured tobacco cessation as a primary or secondary outcome, and were primarily delivered using mobile phone (text or app-based) messaging. Data were extracted on fields pertaining to study and intervention characteristics and study quality was assessed using the Effective Public Health Practice Project tool. Screening, extraction and quality assessment were conducted by two independent reviewers. Results Of 606 unique records, 12 articles were included. The majority of studies were methodologically weak. Methodological limitations included small sample sizes, short follow-up durations and use of self-reported outcomes. Most evaluations were conducted in upper middle-income countries with urban, adult smokers intending to quit smoking. Approximately half the interventions were bidirectional (enabled two-way messaging) and fully automated. Almost all interventions were delivered via SMS. Treatment offerings of the intervention and control groups varied widely. Conclusions More rigorous large-scale randomized controlled trials are needed to conclusively establish the efficacy of mCessation interventions in LMICs. Interventions also need to be tested across more diverse populations and settings. Future studies should test the relative effectiveness of different intervention characteristics.
Mineralization of Biomaterials for Bone Tissue Engineering

Mineralized biomaterials have been demonstrated to enhance bone regeneration compared to their non-mineralized analogs. As non-mineralized scaffolds do not perform as well as mineralized scaffolds in terms of their mechanical and surface properties, osteoconductivity and osteoinductivity, mineralization strategies are promising methods in the development of functional biomimetic bone scaffolds. In particular, the mineralization of three-dimensional (3D) scaffolds has become a promising approach for guided bone regeneration. In this paper, we review the major approaches used for mineralizing tissue engineering constructs. The resulting scaffolds provide minerals chemically similar to the inorganic component of natural bone, carbonated apatite, Ca5(PO4,CO3)3(OH). In addition, we discuss the characterization techniques that are used to characterize the mineralized scaffolds, such as the degree of mineralization, surface characteristics, mechanical properties of the scaffolds, and the chemical composition of the deposited minerals. In vitro cell culture studies show that the mineralized scaffolds are highly osteoinductive. We also summarize, based on literature examples, the applications of 3D mineralized constructs, as well as the rationale behind their use. The mineralized scaffolds have improved bone regeneration in animal models due to the enhanced mechanical properties and cell recruitment capability making them a preferable option for bone tissue engineering over non-mineralized scaffolds.
Is the Phone Mightier than the Virus? Cell Phone Access and Epidemic Containment Efforts

This paper examines the impact of mobile phone access on the containment of an epidemic. Combining proprietary data on cellphone towers and disease cases during the 2014 Ebola epidemic in Liberia, we estimate a high-resolution radio-wave propagation model to predict signal strength. Comparing villages at the margin of the signal strength threshold required for coverage, we uncover a 10.8 percentage point reduction in the likelihood of a case in villages with coverage. Results from a novel survey collected following the epidemic suggest that this is mostly explained by cellphone access facilitating emergency care provision rather than improving access to information.
Can a Global Bioethical Lens Engender Color Blindness? An Examination of Public Health Disasters.

One of the central characteristics of public health disasters (PHDs) is the rapid overlapping of different needs and priorities that require making critical choices that inevitably elicit conflicti...
Partitioned Learned Bloom Filters

Bloom filters are space-efficient probabilistic data structures that are used to test whether an element is a member of a set, and may return false positives. Recently, variations referred to as learned Bloom filters were developed that can provide improved performance in terms of the rate of false positives, by using a learned model for the represented set. However, previous methods for learned Bloom filters do not take full advantage of the learned model. Here we show how to frame the problem of optimal model utilization as an optimization problem, and using our framework derive algorithms that can achieve near-optimal performance in many cases.
The Epidemiology of Psoriatic Arthritis over 5 Decades: A Population-Based Study

OBJECTIVE To determine the incidence of psoriatic arthritis (PsA) in a US population and describe trends in incidence and mortality over 5 decades. METHODS The previously identified population-based cohort that included Olmsted County, Minnesota residents ≥18 years of age who fulfilled PsA criteria during 1970-1999 was extended to include patients with incident PsA during 2000-2017. Age- and sex-specific incidence rates and point prevalence, adjusted to the 2010 US White population, were reported. RESULTS There were 164 incident cases of PsA in 2000-2017 (mean ± SD age 46.4 ± 12.0 years; 47% female). The overall age- and sex-adjusted annual incidence of PsA per 100,000 population was 8.5 (95% confidence interval [95% CI] 7.2-9.8) and was higher in men (9.3 [95% CI 7.4-11.3]) than women (7.7 [95% CI 5.9-9.4]) in 2000-2017. Overall incidence was highest in the 40-59 years age group. The incidence rate was relatively stable during 2000-2017, with no evidence of an overall increase or an increase in men only (but a modest increase of 3% per year in women), compared to 1970-1999 when a 4%-per-year increase in incidence was observed. Point prevalence was 181.8 per 100,000 population (95% CI 156.5-207.1) in 2015. The percentage of women among those with PsA increased from 39% in 1970-1999 and 41% in 2000-2009 to 54% in 2010-2017 (P = 0.08). Overall survival in PsA did not differ from the general population (standardized mortality ratio 0.85 [95% CI 0.61-1.15]). CONCLUSION The incidence of PsA in this predominantly White US population was stable in 2000-2017, in contrast to previous years. However, an increasing proportion of women with PsA was found in this study.
Comment of Proposed Department of Labor Regulations on ESG Investing, Prudence and Loyalty

DOL’s proposed regulations about ERISA’s fiduciary duties of prudence and loyalty weaken the protection of America’s workers and retirees. Accordingly, these proposed regulations should be amended to delete the imprudent, unproven and ambiguous term “ESG,” to add more balanced examples which reduce misperceptions of ERISA’s fiduciary duties, and to expunge altogether the concept of tie-breaking which violates the duty of loyalty by encouraging the pursuit of collateral benefits. The fundamental claims of ESG advocates are economically implausible. Such advocates assert that they consistently outperform and manipulate competitive markets. This claim is unpersuasive. ESG proponents assert that a person making an ESG investment is overriding the market’s allocation of resources to pursue a greater good. This claim is economically unconvincing. When a self-declared ESG-investor sells a stock in a competitive market,another investor without her qualms buys it. This is simply a game of musical chairs which, while it makes the ESG-investor feel better, shuffles ownership without altering the market-driven allocation of resources. The other major claim of ESG advocates is that ESG investing, with its often high fees and active management, can consistently outperform competitive markets. This claim too is economically unpersuasive. If a corporation’s superior governance or more humane labor practices improve a corporation’s financial prospects, the corporation’s stock price will capture that projected income. A conventional, passive investment device, such as a low fee index fund, will reflect that increased value without invoking the ESG label and without paying fees for ESG investing services. It is implausible that ESG funds will consistently outperform competitive markets in which prices efficiently reflect corporation’s projected earnings including projected income stemming from so-called ESG factors. DOL’s proposed regulations improperly perpetuate and liberalize the unpersuasive canon of “tie-breaking” and thereby jeopardize the retirement assets of workers and retirees. The fiduciary duty of loyalty requires exclusive consideration of participants’ welfare – even in the face of so-called “ties.”Under the proposed regulations, fiduciaries desiring to pursue otherwise proscribed collateral benefits will, deliberately or inadvertently, be encouraged to declare ties to free themselves from the duty of loyalty and its prohibition on the pursuit of third party benefits. Contrary to the teaching of the proposed regulations, the exacting duty of loyalty is not suspended in the presence of “ties.”
A trace-based evaluation of adaptive error correction for a wireless local area network

Wireless transmissions are highly susceptible to noise and interference. As a result, the error characteristics of a wireless link may vary widely depending on environmental factors such as location of the communicating systems and activity of competing radiation sources, making error control a difficult task. In this paper we evaluate error control strategies for a wireless LAN. Based on low-level packet traces of WaveLAN, we first show that forward error correction (FEC) is effective in recovering from bit corruptions and that packet length adjustment can reduce packet truncation. However, as expected, fixed error control policies can perform very poorly, because they either introduce too much overhead in “good” environments or are not aggressive enough in “bad” environments. We address this problem through adaptive error control, i.e., error control policies that adapt the degree of FEC redundancy and the packet size to the environment. The effectiveness of adaptive error control depends on the characteristics of the error environment, e.g., the type of errors and the frequency with which the error environment changes. Our evaluation shows that adaptive error control can improve throughput consistently across a wide range of wireless LAN error environments. The reason for this effectiveness is that changes in the error environemtn are often caused by human mobility-related events such as the motion of a cordless phone, which take place over seconds, while adaptation protocols can respond in tens of milliseconds. Evaluating adaptive error control in a wireless environments is challenging because repeatable experiments are difficult: the wireless environment cannot easily be isolated and the adaptation process itself changes the environment, which may make trace-based evaluation difficult. We introduce a trace-based evaluation methodology that deals appropriately with changes in packet content and size.
Outline of power modulator work supported by DOE SBRI grants

Each year, the Department of Energy funds grants for development of ideas in a variety of topics, some of which are associated with power modulator research. An initial Phase I grant allows the proposed research to be fleshed out with some preliminary hardware testing, and sets up the Phase II application which, if approved, funds the main research. For several years, various aspects of solid-state modulators have been the subjects of these grants. The renewed interest in gridded high power klystron designs has called for the development of new pulsed energy delivery systems that are not strictly modulators, but perform the same functions. This presentation reviews the status of presently funded SBIR grants that involve power modulator concepts or supporting component development, and gives a synopsis of the awards for 2002.
Origin, Specification, and Plasticity of the Great Vessels of the Heart

The pharyngeal arch arteries (PAAs) are a series of paired embryonic blood vessels that give rise to several major arteries that connect directly to the heart. During development, the PAAs emerge from nkx2.5-expressing mesodermal cells and connect the dorsal head vasculature to the outflow tract of the heart. Despite their central role in establishing the circulatory system, the embryonic origins of the PAA progenitors are only coarsely defined, and the factors that specify them and their regenerative potential are unclear. Using fate mapping and mutant analysis, we find that PAA progenitors are derived from the tcf21 and nkx2.5 double-positive head mesoderm and require these two transcription factors for their specification and survival. Unexpectedly, cell ablation shows that the tcf21+; nkx2.5+ PAA progenitors are not required for PAA formation. We find that this compensation is due to the replacement of ablated tcf21+; nkx2.5+ PAA cells by endothelial cells from the dorsal head vasculature. Together, these studies assign the embryonic origin of the great vessel progenitors to the interface between the pharyngeal and cardiac mesoderm, identify the transcription factor code required for their specification, and reveal an unexpected plasticity in the formation of the great vessels.
Studies on polynucleotides: LXXXV. Partial purification of an amber supressor tRNA and studies on in vitro suppression

Abstract The serine-specific amber suppressor tRNA of Escherichia coli cells carrying the suI+ gene—a minor serine-tRNA species—has been partially purified. In vitro studies with the tRNA obtained show binding of seryl-tRNA to ribosomes in the presence of UAG and also poly rUAG-dependent polyserine formation. In in vitro protein synthesis experiments with RNA of an amber mutant of bacteriophage f2 as messenger, 100% suppression could be achieved by increasing the concentration of the purified suppressor tRNA. Taking a decrease in suppression in this system as an assay for chain termination, no evidence for a chain-terminator tRNA was obtained. Crude tRNA of E. coli cells carrying the amber suppressor gene suIII+ showed in vitro suppression in f2am RNA-directed protein synthesis.
An exotic shuffle relation for multiple zeta values

In this short note we will provide a new proof of the following exotic shuffle relation of multiple zeta values: Open image in new windowThis was proved by Zagier when n = 0, by Broadhurst when m = 0, and by Borwein, Bradley, and Broadhurst when m = 1. In general this was proved by Bowman and Bradley. Our new idea is to use the method of Borwein et al. to reduce the above general relation to some families of combinatorial identities which can be verified by Zeilberger’s algorithm [9, 10] that is part of the WZ method.
Statistical Inference by Minimal Bures Distance

We have developed, over the past years, a general theory of statistical inference in quantum mechanics1-6 that has now reached a stage in which a presentation based on first principles seems appropriate.
Application of an approximate R-N-G theory to a model for turbulent transport with exact renormalization

The important practical problem of “eddy diffusivity” and renormalization for turbulent transport is discussed. Then a simple model for turbulent transport with rigorous renormalization developed recently by the authors is described. The simple form of the model problem is deceptive; the renormalization theory for this problem exhibits a remarkable range of different phenomena as parameters in the velocity statistics are varied. Thus, the model problem is an interesting test problem for renormalized perturbation theories. In this paper the approximate R-N-G method of Yakhot and Orszag is applied to this exactly solvable model problem and developed in a detailed fashion. The predictions of the approximate R-N-G theory are compared with the exact renormalization theory. In one of the four different regions of nontrivial renormalization the R-N-G theory is exact both for predicting the anomalous scaling exponents and the Green’s function for the equation for eddy diffusivity. The reasons explaining this spectacular success are given in Section 4. For the other three regions, the anomalous scaling exponents and Green’s function predicted by R-N-G are a rather poor approximation to the actual renormalization theory. However, in the one region adjacent to the mean field boundary, the R-N-G theory predicts the first order Taylor expansion of the scaling exponent in agreement with the expected behavior of an e-expansion procedure from critical phenomena.
Somatic Flower-Color Variations and Morphological Changes Induced by C14 in the Snapdragon, Antirrhinum Majus

The genetic and morphological effects of radiocarbon when incorporated into plants of the common snapdragon were investigated. Plants of an F/sub 1/ hybrid heterozygous for flower color and plants of the variety Windmillers Lilac were exposed to atmosphers containing carbon dioxide enriched with C/sup 14/O/sub 2/. The estimated radiation dosages were phase specific activities of 4, 25, 150, and 900 mu c per gram carbon, respectively. The frequency of somatic mutations increased from 0.61 mutant areas per flower in controls, to phase activities of 4, 25, 150, and 900 mu c per gram carbon, respectively. The relationship between air-phase specific activity and frequency of mutant areas appeared to be linear at air-phase specific activities from 25 to 900 mu c per gram carbon; the efficiency of radiocarbon treatment was greatest at 4 mu c per gram carbon. Only two phenotypic classes of mutant areas, pink and white, were classified accurately. Neither the pink nor the white areas were attributed to mutation at specific loci. On the average, pink mutations were observed 7.5 times as frequently as white. No morphological changes in plants of the F/sub 1/ hybrid and Windmillers Lilac were observed at the three lower air-phase specific activities. Plantsmore » exposed to the 900 mu c per gram carbon air-phase activity exhibited reduced lateral branching and flower production, increases in leaf thickness, stem diameter, plant height, abnormalities in flowers, and dichotomous branching of the main stem. Comparisons with other results indicate that radiocarbon treatment was slightly more effective than equivalent amounts of ionization from chronic gamma irradiation in producing certain morphological changes. Radiocarbon and chronic gamma irradiation were not shown to differ in effect in the induction of somatic flower color mutations in snapdragons. (auth)« less
Structural materials: metals, ceramics, polymers and composites

Structural materials are improving at a rate not hitherto seen, and perceptions of the virtues of one material in relation to another may significantly affect the economies of nations. Improved purity and chemical control during refining have enhanced the properties of some steels, aluminium and magnesium. New processes have enabled parts to be cast of a complexity, thin section and cost that were previously impossible. High–strength low–alloy steels are increasingly used in automotive applications. Some aluminium alloys are approaching the strength of titanium alloys at high temperature. New surface coatings are being used to minimize corrosion. Ceramics are finding new applications as abrasives, as heat shields, as containers for molten metals and as high–strength structural materials. Zirconia alloyed with other materials can be made to be crack resistant, and there are signs that increasing use will be made of ceramics under tensile stress in high– temperature environments. Polymers are increasingly being used as structural materials (e.g. in airframe construction); often the material is a blend of one material in a matrix of another. High–performance composites including metal–matrix composites and ceramic– ceramic composites are showing considerable promise for the future.
Molecular cloning and expression in Escherichia coli K-12 of chromosomal genes determining the O7 lipopolysaccharide antigen of a human invasive strain of E. coli O7:K1.

We have cloned and studied the expression in Escherichia coli K-12 of chromosomal rfb genes determining the biosynthesis of the O7 lipopolysaccharide (LPS) antigen from E. coli K1 strain VW187. Two E. coli K-12 strains carrying recombinant cosmids gave positive coagglutination reactions with protein A-rich staphylococcal particles bearing an O7-specific rabbit polyclonal antiserum. Silver-stained polyacrylamide gels of total membranes extracted with hot phenol showed O side chain material which had O7 specificity as determined by immunoblotting experiments. However, the amount of O7 LPS expressed in E. coli K-12 was considerably lower than that produced by the wild-type strain VW187. Deletion and transposition experiments identified a region of about 17 kilobase pairs which is essential for the expression of O7 LPS. The existence of homologies between the O7 LPS genes and other E. coli O side chain genes was investigated by Southern blot hybridization experiments. An O7-specific probe fragment of 15 kilobase pairs did not hybridize to genomic DNA digests of E. coli strains belonging to several different O types, demonstrating that the O7 LPS genes are unique. Images
Cholinesterase research at the National Institutes of Health, USA

Presented below is a brief description of research supported by the National Institutes of Health (NIH) on cholinesterases that was discussed at the IXth International Meeting on Cholinesterases in Suzhou, China. It is a partial description of the research conducted by researchers at academic and other institutions supported by the NIH, and by some of the researchers in NIH intramural laboratories. It does not represent a comprehensive survey of all research supported by the NIH related to cholinesterases, but rather a brief discussion of some of the studies discussed at the IXth International Meeting on Cholinesterases. The article describes exciting basic, translational and clinical research on therapies for neurological and other diseases. In addition, cholinesterases that may treat substance abuse are discussed, and pesticide and chemical warfare agents that inhibit cholinesterases are highlighted as part of the NIH portfolio. It is the intent of this article to share with the international community some of the research being supported by the NIH on cholinesterases that complements many of the studies being conducted elsewhere. The information was obtained only from published articles or from abstracts available to the public within the NIH CRISP database (http://crisp.cit.nih.gov/).
Catalase mediated conversion of cyanamide to an inhibitor of aldehyde dehydrogenase

A minor pathway for cyanamide metabolism catalyzed by catalase is responsible for the conversion of cyanamide to an inhibitor of aldehyde dehydrogenase. Catalase itself is also inhibited by cyanamide. Both the activation of cyanamide by catalase and the inhibition of catalase by cyanamide were blocked in vivo by ethanol pretreatment, suggesting that these two processes are closely linked. Like other catalase oxidation reactions, the catalase mediated activation of cyanamide was inhibited by 3-amino-1,2,4-triazole in vivo and sodium azide in vitro. The relative formation of the active cyanamide metabolite was assessed in vitro by following the loss of yeast aldehyde dehydrogenase activity with time. Inhibition of the yeast enzyme by activated cyanamide was dependent on NAD+ or NADP+, a requirement not fulfilled by NADH or NADPH. Although H2O2 inhibited yeast aldehyde dehydrogenase in vitro and cyanamide inhibited hepatic catalase in vivo, the possible in hepatic H2O2 concentration following cyanamide administration does not account for the effects of cyanamide on ethanol metabolism. While the cyanamide activating enzyme has been identified as catalase, the reaction products of this reaction and, in particular, the structure of the active metabolite involved in the inhibition of aldehyde dehydrogenase remain unknown.
The hatching of gypsy moth eggs, a phenological model

Abstract The skewed course of hatching of gypsy moth eggs is represented by a mathematical model embodying the conception that the eggs begin at location 0 in development space and progress at a rate that is the reciprocal of the time when the first eggs hatch because they reach location 1 in space. During their progress, a daily fraction is delayed for a period and then progresses again from the location in space from which it was delayed. Theoretically, the course of hatching is represented by a Poisson function, with the usual mean replaced by the product of the daily fraction delayed and the time of first hatch. A time referred to the time of first hatch and adjusted for the period of delay replaces the usual number whose frequency is calculated. Skewness significantly exceeded the expected 0 of the Normal curve in 79% of 91 experiments at steady temperature, whereas it exceeded the expected skewness of the Poisson in only 35%. The times of first hatch and of delay and the daily fraction delayed changed in an orderly fashion from 12 to 33°C. In 43 experiments with changing temperature in the laboratory, the course of hatching was predicted by numerical integration of the parameters observed at steady temperature. The standard deviation of the difference between observation and prediction was 2 3 day for the time of first hatch and the mean time of individual hatches; it was 1 2 3 days-squared for the variance and 1 2 unit for the skewness. In six outdoor experiments from spring to autumn, the entire courses of hatching were predicted reasonably well, and the means were predicted more consistently than by a method of degree-days.
Bulk viscosity in the Navier–Stokes equations

Abstract This article discusses the physics associated with the bulk viscosity coefficient μ b as it appears in the compressible Navier–Stokes equations. Thus, the active rotational and vibrational modes of a polyatomic molecule are discussed with emphasis on the importance of local thermodynamic equilibrium. This condition is necessary if μ b is to only depend on the thermodynamic state, as required for the Navier–Stokes equations. A new perturbation formulation is provided for the absorption and dispersion coefficients and the entropy production that holds even when μ b greatly exceeds the shear viscosity, as is the case for gases such as CO 2 . A comparison for CO 2 shows excellent agreement between exact results and the low-frequency formula used for the absorption coefficient. This agreement stems from a large value for the Peclet number.
Emergent complex states in bilayer graphene

Symmetries play a critical role in physical systems. The famous Noether's theorem states that a continuous symmetry of a system has a corresponding conserved physical quantity. For example, a physical system that is invariant in position and time must obey conservation of linear momentum and energy, respectively. The breaking of symmetries has equally important consequences—some examples being the Higgs boson, superconductivity, and ferromagnetism. Electrons in graphene, a monolayer sheet of hexagonally bonded carbon atoms, exhibit an approximate fourfold symmetry due to the two equivalent atoms per unit cell and spin degeneracy. The unusual electronic transport properties that result when a magnetic field is applied reflect these symmetries ( 1 – 3 ). The two layers of carbon atoms in bilayer graphene provide an extra degree of freedom, making it an even richer system for complex electronic states to emerge. Using different measurement techniques, a trio of studies in this issue—by Kou et al. ( 4 ) on page 55, Lee et al. ( 5 ) on page 58, and Maher et al. ( 6 ) on page 61—have elucidated the nature of these exotic broken-symmetry states.
Where Has All the Money Gone?: Arnold on the Degeneration of Market Socialism

This paper is a defense of the worker-control model of market socialism. Criticizing a recent argument by N. Scott Arnold, I show that he failed to demonstrate that, in the worker-control model of market socialism, workers are bound to lose the right to a share in the firm's income.
The Implications of the Pre-War Philippine Experience for Peace Research

In the years before World War II, the Philippines attempted a defense plan that was, according to the officials in charge, explicitly modeled on Switzerland's approach to defense. The plan was a failure, for the Philippines was conquered and suffered greatly during the war. This article argues, however, that the Philippine defense plan was inconsistent in fundamental respects with the basic principles of the Swiss approach. The Philippine defense program did constitute a threat to others; Philippine foreign and economic policies were not neutral between other nations; positive inducements were not provided to discourage attack; and the nature of Philippine society did not assure the high morale of the citizenry.
Dose-titrated, double-blind, cross-over comparison of a selective beta-blocker and methyldopa in the treatment of hypertension.

The efficacy and toxicity of tolamolol and methyldopa in hypertensive patients has been compared by a dose-titrated, double-blind, cross-over study. Thirteen patients completed the trial. Within the dose ranges investigated (tolamolol — 300 mg/day — 900 mg/day; methyldopa — 750 mg/day — 2250 mg/day) both drugs produced significant falls in laying and standing, systolic and diastolic blood pressures. Although the hypotensive effects of methyldopa were more marked than tolamolol, these only achieved conventional (P<0.05) levels of significance for lying blood pressure. There were no objective changes in haematological or biochemical indices during treatment with either drug, but patients complained of tiredness, weak limbs and mouth dryness significantly more during methyldopa treatment, than during either placebo or tolamolol therapy.
The determination of lactic dehydrogenase with a tetrazolium salt.

Abstract A colorimetric method for the measurement of lactic dehydrogenase activity has been described, utilizing phenazine methosulfate as an intermediate agent for electron transfer from DPNH to a tetrazolium salt (INT). The use of gelatin to keep the formazan in colloidal suspension provided the added advantage of improving electron transfer via a phenazine methosulfate gelatin complex over that obtained with soluble diaphorase or phenazine methosulfate alone. Several compounds were studied for their ability to act as intermediate electron-transfer reagents, but none were superior to phenazine methosulfate. The sensitivity of the new method is comparable to others measuring either DPNH or pyruvate; its advantages are those of brevity and simplicity. Normal human sera were found to contain from 50 to 100 units of lactic dehydrogenase. The importance of avoiding hemolysis of the blood has been re-emphasized, and the possibility has been demonstrated that a 10–15% overestimation may occur due to hemolysis even when gross hemolysis cannot be recognized.
Multiphoton ionization of hydrogen in ultrastrong laser fields

The three previous calculations of this process yield differing results for the transition rate. We show the relations between them and difficulties with each of them. One difficulty is that the finite spatial extent of the laser field has been omitted. It is also found that a laser field, which is sufficiently intense to be labeled ultrastrong, makes the electron move relativistically so that it becomes necessary to use Volkov states to describe the electron in the laser field. The transition rate is obtained, with the use of a C${\mathrm{O}}_{2}$ laser as an example, and it is found that the transition rate rises as the laser intensity rises. This is a consequence of the use of relativistic kinematics and is not true nonrelativistically.
Enoximone (MDL 17,043) for stable, chronic heart failure secondary to ischemic or idiopathic cardiomyopathy

To examine the efficacy and safety of enoximone for treatment of patients with chronic, clinically stable cardiac failure secondary to ischemic or myopathic heart disease, 31 patients were enrolled into an early phase II trial. The hemodynamic response to intravenous and oral enoximone was assessed and compared with the response to dobutamine therapy (5 to 10 μg/kg/min). Maximal O2 uptake, an objective measure of effort tolerance, was serially monitored. Intravenous (1 to 2 mg/kg) and oral (1 to 2 mg/kg) enoximone improved (p < 0.05) cardiac index while reducing right atrial and wedge pressures to a greater extent than dobutamine. The salutary hemodynamic response to oral enoximone was sustained for 6 to 8 hours and was not associated with subacute drug tolerance. Maximal O2 uptake was increased (p < 0.05) at 2, 4, 8, 12, 24 and 52 weeks of oral enoximone therapy (1.4 ±0.5 mg/kg every 8 hours) while radionuclide ejection fraction at 65 weeks increased (p < 0.05) from baseline (39 ± 16% vs 30 ± 9%). Nine patients, 8 of whom were in functional class III or IV on enrollment, died after a mean of 18 weeks: 4 from cardiac failure and 5 suddenly. Two patients had adverse gastrointestinal effects. Oral enoximone (1 to 2 mg/kg every 8 hours) appears to be useful in the short- and long-term management of clinically stable, chronic cardiac failure. Controlled phase III trials are warranted.
Influence of anesthetics on endogenous and recombinantly expressed G protein-coupled receptors in the Xenopus oocyte.

Abstract 1. The oocyte of the African clawed toad (Xenopus laevis) offers a reliable, sensitive and disease resistant system to investigate recombinantly and endogenously expressed Ca2+ signaling G protein-coupled receptors and their intracellular signaling pathways. 2. To study receptor induced Ca2+ release, two-electrode voltage clamping can quantify a Ca2+-activated transmembrane Cl− current. Intracellular steps of the signaling pathway can be inhibited by injections of EDTA or heparin into the oocyte. Components of the intracellular pathway can be activated directly by GTPγS or IP3 injection. 3. We have investigated the effects of volatile, local and i.v. anesthetics on the signaling properties of the endogenous lysophosphatidate receptor and on mammalian receptors expressed recombinantly by intracellular injection of the encoding mRNA or cDNA. A number of receptors are sensitive to these anesthetics. Anesthetics interact with muscarinic, thromboxane A2 and lysophosphatidate signaling. 4. Investigations of the intracellular pathways revealed that the receptor or the receptor-G protein coupling is affected primarily and that mechanisms further downstream are not influenced by the various types of anesthetics.
Impact of Fluoroquinolones on the Gastrointestinal Flora

A number of studies have evaluated the effect of fluoroquinolones on fecal flora. The results of these studies have consistently shown marked suppression or elimination of gram-negative facultative bacteria. The effect on gram-positive bacteria is more variable, with slight to moderate suppression reported most frequently. Total fecal anaerobes have generally been unchanged, although some anaerobic species have been moderately suppressed. The effect on facultative gram-negative bacteria can be explained by high fecal levels of quinolones and very low MICs for most of the organisms. The general lack of effect of anaerobes may be due to the higher MICs and an inoculum effect on the MBCs that is caused by the large number of organisms (10(9)-10(11) colony-forming units/g) characteristically found in feces.
Kinase Inhibitors as Potential Therapeutics for Acute and Chronic Neurodegenerative Conditions

Kinases, which number > 500 in humans, are a class of enzymes that participate in an array of important functions within normal cellular physiology and during various pathological conditions. Due to the key role of kinases in the regulation of all aspects of cellular signaling and the well established contribution of kinase dysregulation to the etiology of many human pathologies, the development of kinase inhibitors has emerged as a therapeutic strategy for the treatment of human disease, including most notably oncology. Difficulties generating selective inhibitors have hampered their use in other therapeutic areas with less tolerance for off-target effects. However, with an increasing understanding of kinase structures and with the advent of newer inhibitor design strategies more highly selective inhibitors are beginning to emerge. This has prompted interest in utilizing kinase inhibitors in therapeutic areas beyond oncology, including acute and chronic neurodegenerative conditions for which disease modify therapies are lacking. This review provides a background in acute (i.e. brain ischemia and traumatic brain injury) and chronic (i.e. Alzheimer's, Parkinson's, Huntington's disease, amyotrophic lateral sclerosis and multiple sclerosis) neurodegenerative conditions. Then, the role of several kinase (i.e. JNK3, p38 MAPK, ERK, PKC, ROCKII, GSK3, Cdk5, MLK, EphB3 kinase, RIP1 kinase, LRRK2, TTBK1, ASK1, CK, DAPK, and PKN1) that could serve as potential therapeutic targets for these maladies are reviewed.
Non-surgical Management of Early Breast Cancer in the United Kingdom: Follow-up

Follow-up of operable breast cancer patients takes up a significant proportion of British oncologists' time, with 90% seeing 5-50 patients each week. Procedures vary greatly, but, in patients treated by surgery and radiotherapy, care is usually shared, with alternating visits to see each team. Currently, the general practitioner has sole responsibility for follow-up in less than 3% of patients. They tend to be followed up in general, rather than specialist, clinics. There is almost universal agreement that routine blood tests, radiographs and scans are not indicated as part of routine follow-up, but the role of mammography in evaluating an irradiated breast remains a source of debate. Just over a half of the oncologists surveyed order baseline mammography of both treated and contralateral breasts, usually between 6 and 12 months after local excision and radiotherapy, with further follow-up 1-3-yearly thereafter. Ten per cent of the participating oncologists never suggest follow-up mammography. Patients tend to be followed in oncology clinics at 3-4-monthly intervals for the first 2 years, 6-monthly in the third and fourth years and, thereafter, yearly. Fifteen per cent of oncologists discharge patients at 5 years, with the discharge rate rising to 43% at 10 years; around one-third modify follow-up according to the age of the patient. The aims of follow-up were seen to include detection of curable disease, but other goals were perceived as equally important (e.g. detection of iatrogenic problems, audit, counselling, education and the provision of early palliation of incurable and metastatic disease. Breast cancer is no longer seen as an absolute contraindication to either pregnancy or the use of hormone replacement therapy (HRT); however, oncologists are uncertain about the appropriate use of HRT, either alone or with tamoxifen. This audit highlights a number of research areas: the identification of the appropriate site and skill-mix for follow-up of patients; clarification of the aims and attitudes to follow-up by both patients and health care professionals; the use of breast imaging; and the role of HRT.
Cycloaddition of Cyclopentadiene to 3-Deoxy-1,2:5,6-di-O-isopropylidene-alpha-D-erythro-hex-3-enofuranose. Synthesis and Representative Chemistry of 1,6-Anhydro-2,3-dideoxy-beta-D-glycero-hex-2-enopyran-4-ulose ("Isolevoglucosenone").

Treatment of d-glucose-derived alkene 4 with cyclopentadiene in the presence of a Lewis acid results in the formation of cycloaddition products 8−11. Evidence is presented to show that these 1,6-anhydro sugar−cyclopentadiene adducts do not arise from rearrangement of 4 to isolevoglucosenone (5) followed by cycloaddition but are the result of Lewis acid-catalyzed rearrangement of alkene 4 to acyclic dienophile 12 followed by addition of cyclopentadiene. Major cycloadduct 8 has been utilized as a source of the enantiomerically pure carbocycles 14−25 by manipulation of the alkene and ketone functions and cleavage of the 1,6-anhydro bridge. In the absence of diene, alkene 4 undergoes rearrangement to enone 5 in 32% yield. Reaction of 5 with several dienes results only in the formation of “bottom-face” adducts 10, 11, 28, and 29, and conjugate addition of either HN3 or Me3COOH is found to be completely stereoselective to afford 30 and 31, respectively. Subsequent manipulation of azide 30 leads to precursors of...
Impaired NO signaling in small pulmonary arteries of chronically hypoxic newborn piglets.

We performed studies to determine whether chronic hypoxia impairs nitric oxide (NO) signaling in resistance level pulmonary arteries (PAs) of newborn piglets. Piglets were maintained in room air (c...
First-principles interatomic potentials for transition-metal aluminides: Theory and trends across the 3d series

In this paper the first-principles generalized pseudopotential theory (GPT) of transition-metal interatomic potentials [J. A. Moriarty, Phys. Rev. B 38, 3199 (1988)] is extended to $\mathrm{AB}$ binary compounds and alloys. For general transition-metal (TM) systems, the GPT total-energy functional involves a volume term, central-force pair potentials, and angular-force multi-ion potentials, which are both volume $(\ensuremath{\Omega})$ and concentration $(x)$ dependent and include all $sp,$ $sp\ensuremath{-}d,$ and $d\ensuremath{-}d$ interactions within local density-functional quantum mechanics. The formalism is developed here in detail for intermetallic systems where $A$ is a simple metal and $B$ is a transition metal and applied to the prominent special case of the transition-metal aluminides ${\mathrm{TM}}_{x}{\mathrm{Al}}_{1\ensuremath{-}x},$ where $sp\ensuremath{-}d$ hybridization is especially important. Emphasis is given to the aluminum-rich $3d$ binary systems for $xl0.30,$ which appear to be well described at the pair-potential level without angular forces and for which the present GPT potentials can be used directly in atomistic simulations. Volume terms and pair potentials for all of the $3d$ aluminides have been calculated and their behavior with atomic number, $\ensuremath{\Omega},$ and $x$ is elaborated through illustrative applications to the cohesive and structural trends across the $3d$ series. More extensive applications to the Co-Al and Ni-Al phase diagrams will be given elsewhere.
Abstract 1860: Protective effect of catechol-O-methyltransferase-mediated 4-hydroxyestradiol metabolism in human renal cell cancers

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Long-term exposure to estrogen and its metabolites may play an important role in renal cell carcinogenesis. Catechol-O-methyltransferase (COMT) participates in the estrogen metabolism pathway by neutralizing toxic substances. Although reduced COMT activity has been suggested to be a risk factor for estrogen-associated cancers, no studies have investigated the biological significance of COMT in the pathogenesis of human renal cell cancers (RCC). Using quantitative PCR, Western blotting and immunohistochemical staining, we initially found that COMT levels are significantly decreased in human RCC tissues and cells suggesting a suppressive role of COMT in tumor development. However, transient over-expression of COMT has no effect on the proliferation, apoptosis and cell cycle progression of RCC cell lines. In contrast, when cells over-expressing COMT are treated with its substrate 4-hydroxyestradiol (4-OHE2), growth is inhibited by apoptotic cell death. We also found that COMT over-expression combined with 4-OHE2 induces up-regulation of growth arrest- and DNA damage-inducible protein ≤ (GADD45α). We further show that down-regulation of GADD45α by a siRNA-mediated approach inhibits cell death, indicating the essential role of GADD45α in the underlying mechanism of COMT action in response to 4-OHE2. Finally, 4-methoxyestradiol (4-ME) fully reproduces the anti-proliferative function of COMT with 4-OHE2 by promoting GADD45α induction. Together, our study shows that COMT in the presence of 4-OHE2 prevents RCC cell proliferation by enhancing apoptosis, and that GADD45α plays a critical role in the COMT-mediated inhibition of RCC. These findings will provide new direction for the biomarker detection and corresponding treatment in the prevention of human RCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1860. doi:1538-7445.AM2012-1860
Response to Dr. McFarland

TO THE EDITOR: In the process of editing the manuscript, the p value as reported by Surawicz et al. was misquoted and should have been 0.04 rather than 0.07. The manuscript should have been referenced as a full article. We regret this error in our editing process.