cssi/SciSciGPT-SciSciNet huggingface dataset:
Epidemiology of HIV/AIDS, hepatitis B, hepatitis C, and tuberculosis among minority injection drug users.

Abstract OBJECTIVE: This article reviews the literature on the impact of HIV/AIDS, hepatitis B and C viruses (HBV, HCV), and tuberculosis on minority drug injectors in the United States. OBSERVATIONS: Injection drug use is a key factor in the transmission of blood-borne pathogens, and HIV disease is exacerbated by tuberculosis infection. Minority drug injectors are disproportionately represented in the national statistics on these infections. Behavioral epidemiologic studies show that both injection-related risk factors years of injecting drugs, type of drug injected, direct and indirect sharing of injection paraphernalia) and sex-related risk factors (lack of condom use, multiple sexual partners, survival sex) are conducive to the spread of HIV, HBV, and HCV. CONCLUSIONS: Two issues must be addressed to halt the spread of HIV infection and hepatitis B and C. The capacity of syringe-exchange programs to refer participants to drug treatment programs and facilitate access to health and social services must be increased. Culturally appropriate behavioral interventions targeting risk behaviors among ethnic and racial minorities, especially women, must be developed and put in place.
Phototropins, other photoreceptors, and associated signaling: the lead and supporting cast in the control of plant movement responses.

Publisher Summary This chapter focuses on light-driven plant movements that occur in response to the perception of changes in light direction, intensity, and/or duration within the near-ultraviolet (UV), wavelengths between 320–390 nm and blue (390 and 500 nm) regions of the electromagnetic spectrum. The most obvious plant movement induced by this portion of the light spectrum is phototropism, directional growth response to directional light cues. Plants also respond to changes in the intensity of incident near-UV or blue light by adjusting the position of chloroplasts (organelles that contain light-harvesting complexes required for photosynthesis) within cells. All of the plant movements reviewed in the chapter require light perception by at least one of two phototropin light sensors. The first phototropin, PHOT1, was identified genetically in a screen for Arabidopsis mutants with altered phototropic responses in low-intensity, directional blue light. The second phototropin, PHOT2, was identified initially by its sequence homology to PHOT1. Phototropins are members of a larger family of proteins known as the “LOV” domain family. The ability of the phototropins to function as near-UV–blue-light receptors is derived from the association (noncovalent in a dark state) of a single flavin mononucleotide (FMN) molecule with each LOV domain, and the unique photocycle that occurs within this chromopeptide. Phototropins are the ‘‘on’’ and ‘‘off’’ switch for phototropism, but other photoreceptors are the ‘‘dimmer’’ switch, controlling the degree of phototropic response. When light is optimal, chloroplasts are scattered within the cell; however, if the light intensity changes, the chloroplasts are relocated to adjust to that change. The isolation of mutants in all phototropins, cryptochromes, and phytochromes have led to a cascade of discoveries and provided powerful tools for elucidating the molecular processes involved in blue light-driven plant movement responses.
Improving buffalo milk.

Abstract: Buffalo are the second largest source of milk supply in the world; world production of buffalo milk exceeds 75 million metric tons per year and is increasing steadily at about 3% per year. Dairy cattle produce 84% of the total milk in the world with an average fat and protein content of 4% and 3.5%, respectively, while the average fat content of buffalo milk is about 8% and the protein content in buffalo milk ranges from 4% to almost 4.5%. Thus, in terms of energy-corrected milk, buffalo milk accounts for about twice the food contribution implied by the volume of buffalo milk produced yearly. Physiologically, buffalo are capable of breeding throughout the year and having a calf every year. However, oestrus detection in buffalo is a problem; while irregular oestrus, and anoestrus lasting three or four months, are rarely seen in modern Western dairy herds, it is a common problem in small, rural buffalo herds, which makes up the majority of the buffalo production in most of the world. There are several important herd management factors that should be considered to improve milk production in buffalo. These include managing the nutritional status of the dam around calving, pre- and post-partum hygiene, good milking management, balanced feeding throughout the year, oestrus detection and artificial insemination, and finally managing thermal stress and improving housing. Buffalo milk can be utilized for manufacture of a wide variety of dairy products. Because of the differences in compositional and physicochemical properties between buffalo and bovine milk, processing technology and equipment designed for cow’s milk may not be suitable for buffalo milk processing. Modifications must be considered for making certain products.
Titrimetric Procedure for Assay of Milk Arylesterase Activity

Abstract The purpose of this investigation was to develop a rapid, simple titrimetric method which could be used to replace the more expensive and time consuming Warburg method for the assay of milk arylesterase (A-esterase) activity. A titrimetric method was selected on the basis of preliminary experimentation. Optimum conditions (e.g., temp, pH, substrate concentration, and time) for the assay of milk A-esterase activity were then investigated. On the basis of these results a standard titrimetric method was suggested. This procedure was then compared with the Warburg method ( r = 0.97, n = 182). The coefficients of variation between duplicate samples were 2.6 and 5.2%, respectively, for the Warburg and titrimetric methods. The precision of the titrimetric procedure was increased (approximately fourfold) by titrating to a constant pH, using a potentiometer instead of phenolphthalein.
Application of residual strength models to finite element analysis in fatigue life estimation of a composite wing spar

An engineering approach is proposed to assess fatigue life of an aircraft composite wing spar. Two different strength degradation models are validated using finite element simulation. Stiffness degradation data is obtained based on unidirectional coupon test results from the literature. A code in the finite element software ANSYS is written that lowers the strength and stiffness in each cycle. Stress redistribution is found in any cycle using new stiffness data, and the model is checked for failure. In order to verify the model, bending fatigue tests are carried out on an unmanned aircraft spar sample. The more accurate model is used in fatigue life assessment of the spar under service loading that is found using MINITWIST algorithm. The results indicate that the proposed approach can be used for design engineers in fatigue life assessment of composite wing structures.
Endocrine Toxicity of Drinking Water Disinfectants. II. Inhibition of Hepatic 5'-Thyroxine Deiodinase by Halogenated Nutrients:

Administration of drinking water treated with chlorine-based disinfectants was shown in prior studies to interfere with thyroid function of laboratory animals. One possible mechanism is that intraalimentary redox interactions between chlorine oxides and organic and inorganic contents of the gastrointestinal tract cause formation of iodinated and chlorinated nutrients. Several halogenated organic molecules generated by this route were shown to vary in their in vivo dehalogenation and clearance. In seeking clues to the etiology of the thyroid effect, the influence of several iodinated and chlorinated amino and fatty acid isomers on 5-deiodination of thyroxine (T4) to triiodothyronine (T3) was studied using rat liver homogenates in this study. Several of the compounds tested inhibited conversion of T4 to T3, with effective concentration comparable to the known inhibitor of the type I 5'-thyroxine deiodinase (5'-TDI). Unexpectedly, iodinated isomers of histidine, and chlorotyrosine appeared to activate rather...
The Postnatal Phenotype of the Human Glut 4 Glucose Transporter Overexpressing Transgenic Mice

The Postnatal Phenotype of the Human Glut 4 Glucose Transporter Overexpressing Transgenic Mice
Health Educator Believability and College Student Self-rated Health

Abstract Objective: To evaluate the self-rated health (SRH) status among college students who reported receiving the majority of their health-related information from health educators. Participants: Students (n = 49,921) who completed the 2006 National College Health Association survey. Methods: Bivariate associations between SRH and the believability of health information received were analyzed. Multiple logistic regression tested the relationship after covariate adjustment. Results: Although a modest correlation (r = .06, p < .0001) existed between the variables, SRH declined as the believability of health information received from health educators ratings became increasingly unfavorable (χ2 = 110.96, p < .0001). After covariate adjustment, the relationship persisted with increased odds of reporting fair/poor health for those who reported the health information received from health educators as “neutral” (odds ratio [OR] = 1.31) or “unbelievable” (OR = 2.25) when compared to those who reported the healt...
Enzymatic conversion of ribonucleotides to deoxynucleotides.

Abstract 1. 1. An assay procedure suitable for detecting deoxynucleotides synthesized from ribonucleotides in cell-free preparations of Lactobacillus leichmannii is described. 2. The enzyme preparations used are not affected by dialysis or storage in the frozen state, and are stimulated by addition of adenosine 5′-triphosphate. 3. Enzyme preparations obtained from cells grown in the presence of vitamin B 12 can convert [ 14 C]adenosine 5′-phosphate or [ 14 C]adenosine 5′-diphosphate to [ 14 C]deoxyadenosine 5′-phosphate plus [ 14 C]deoxyadenosine 5′-diphosphate and [ 14 C]uridine monophosphate to [ 14 C]deoxyuridine monophosphate plus [ 14 C]deoxyuridine diphosphate without change in the isotope distribution in the carbon skeleton of the molecules. Enzymes prepared from cells grown without vitamin B 12 in the media do not catalyze the synthesis of deoxyribose but do catalyze a transfer of adenine of adenosine 5′-diphosphate to deoxyadenosine-containing compounds.
Behavioral and ecophysiological responses of a generalist predator to single- and mixed-species diets of different quality

Prey of different quality can be distinguished by their effects on fitness parameters (e.g., survival, growth, development) of the predator. This paper describes a series of experiments with wolf spiders, Schizocosa sp., designed to analyze the behavioral and physiological mechanisms by which these effects are brought about. Schizocosa responded to prey of inferior quality by developing an aversion. The number of prey encounters needed for the aversion to develop depended on the prey type and the quality of alternative prey available. As expected, fewer low-quality prey were accepted if prey of higher quality were available; however, acceptance was also reduced if alternative prey were of even lower quality. An aversion disappeared within a few hours to about 1 day. Consumption by Schizocosa of even small amounts of some “toxic” prey species reduced growth by inhibiting feeding rate and impairing utilization of food derived from prey of higher quality. These results have implications for understanding the interactions of generalist predators in community food webs.
Comparative studies of several potato seed treatments

Trials during 1943 and 1944 of three commercial root hormones applied as dust to seed potatoes resulted in no increases in yield. Rootone and transplantone were compared in 1943, rootone and tubertone in 1944. Rootone retarded emergence, reduced the stand and appeared to be toxic to sprout growth. Es-Min-E1, a commercial mixture of trace-elements, applied at rates of 50 and 100 pounds to the acre in the row and separate from the regular fertilizer application, showed no benefits. The conclusion is that this relatively infertile highly acid, gravelly loam soil was not lacking in these minor elements.
Deep brain stimulation for treatment of voice disorders.

Summary Objectives Vocal tremor is a common, troublesome disorder that is difficult to treat. Efficacy of deep brain stimulation (DBS) was reported more than a decade ago. Most laryngologists are not familiar with the technique or its potential. This review was undertaken to assemble relevant literature written over the past decade and assess the clinical implications of that literature. Design Literature review. Methods PubMed search from 2002 through 2011. Results A small number of articles on the topic have been identified, some of which appear to provide information of potential clinical importance for voice patients. Conclusion A review of the literature from 2002 through 2011 has revealed several studies supporting the efficacy of DBS as well as adverse consequences of specific technical approaches (such as high-frequency DBS). In the aging population, the prevalence of this voice tremor is likely to increase. We suspect that DBS may be underused; and laryngologists should collaborate with neurosurgeons, speech-language pathologists, and voice scientists to study more extensively the safety and efficacy of DBS for treatment of voice disorders.
The Bell–Evans–Polanyi Principle and the regioselectivity of electrophilic aromatic substitution reactions

Abstract Relative activation energies of competing electrophilic aromatic substitution transition states are shown to correlate precisely with computed relative enthalpy changes leading to the corresponding σ complexes. The correlations manifest the Bell–Evans–Polanyi Principle, which may be summarized by the relationship, Ea = m(ΔH) + I. Close correlation occurs for a variety of reactions and reactivities, but correlation does not occur for nitration of toluene, a case known to be exceptional. The correlations imply that activation energies control regioselectivity, and that the properties of the competing transition states resemble those of the σ complexes.
Familial aortic aneurysms

Thoracic aortic aneurysms and dissections can occur in families with autosomal dominant inheritance. Mutations in the fibrillin-1 gene on chromosome 15 cause Marfan syndrome (MFS), a known cause of familial aortic aneurysms and dissections. Affected individuals have phenotypic stigmata involving the skeletal, ophthalmologic and other systems. Mutations in the type III procollagen gene cause the vascular type of Ehlers-Danlos syndrome (EDS IV), which can include aneurysms that involve the aorta and other arteries, but account for a small minority of aortic aneurysms. Affected individuals have characteristic skin and joint findings. Families with no external phenotypic stigmata of connective tissue disorders have been reported as cases of Erdheim disease or annuloaortic ectasia. The causative gene(s) have not yet been identified. We report a family in which aortic aneurysms occurred in several family members who have no phenotypic findings suggestive of either MFS or EDS IV. None of the affected individuals have tall stature, dislocated ocular lenses, scoliosis or pectus deformities. The proband (II-1) was thought to be in good health until she developed chest pain at age 56 and died of a dissecting aneurysm of the ascending aorta that ruptured into the pericardial space. Microscopic examination of the aorta showed cystic medial necrosis. She had 5 children, 3 of whom also had thoracic aortic aneurysms. Her oldest son (III-1) and older daughter (III-4) have had prophylactic surgery at ages 60 and 49. The younger daughter (III-5) had emergency surgery after aortic rupture during catheterization at age 48. A skin biopsy was obtained from the older daughter and dermal fibroblasts explanted. Metabolic labeling studies done in triplicate showed diminished amounts of fibrillin-1 deposited into the matrix by the patient's cells when compared with controls. A similar defect in fibrillin-1 incorporation is observed in cells from MFS patients. Linkage and mutation studies are in progress to determine if the phenotype is due to a FBN1 mutation or a mutation in another gene that disrupts fibrillin-1 deposition in the matrix.
Effects Of Blebbistatin And BDM (2,3-Butanedione Monoxime) On The Short-range Mechanical Properties Of Murine Diaphragm Muscle Fibers

Blebbistatin (BLEB) and 2,3-butanedione monoxime (BDM) are well-know inhibitors of myofilament force production and useful tools in structural and functional studies of cell motility and muscle contraction. In this study, we investigated the effects of BLEB and BDM on the short-range mechanical properties of single chemically permeabilized murine diaphragm fibers. BLEB and BDM were used in separate sets of experiments to reduce isometric force in saturating Ca2+ solution to approximately 50% of the control value. Muscle fibers were subjected to repeated triangular length changes (paired ramp stretches/releases, 0.04 l0, 0.33 l0 s−1) imposed under fiber length control in solutions with free Ca2+ concentrations ranging from pCa 9.0 to pCa 4.5. Short-range stiffness values were calculated from the slopes of regression lines fitted to the first 15 ms of XY plots of force against muscle length for each stretch response and expressed as Young's Moduli. Analysis of results obtained in control Ca2+ solutions (without BLEB or BDM) showed that short-range stiffness increased proportionately with the level of isometric force. Experiments performed with BLEB showed that short-range stiffness declined in proportion with the reduction in isometric force (no change in the stiffness/force ratio). In contrast, BDM produced a disproportionately large decrease in isometric force (that is, the stiffness/force ratio increased in the presence of BDM, ANACOVA test, p<0.001). These results support the hypothesis that BLEB and BDM reduce isometric force in skeletal muscles by different mechanisms. BLEB seems to prevent myosin heads from attaching to the thin filament while BDM probably reduces force by decreasing the rate at which myosin heads undergo tension-generating biochemical transitions.
Discussion of Identification, Estimation and Approximation of Risk under Interventions that Depend on the Natural Value of Treatment Using Observational Data, by Jessica Young, Miguel Hernan, and James Robins.

Young, Hernan, and Robins consider the mean outcome under a dynamic intervention that may rely on the natural value of treatment. They first identify this value with a statistical target parameter, and then show that this statistical target parameter can also be identified with a causal parameter which gives the mean outcome under a stochastic intervention. The authors then describe estimation strategies for these quantities. Here we augment the authors' insightful discussion by sharing our experiences in situations where two causal questions lead to the same statistical estimand, or the newer problem that arises in the study of data adaptive parameters, where two statistical estimands can lead to the same estimation problem. Given a statistical estimation problem, we encourage others to always use a robust estimation framework where the data generating distribution truly belongs to the statistical model. We close with a discussion of a framework which has these properties.
Redescription of a Little Known Crangonid Shrimp, Metacrangon Laevis (Yokoya, 1933) (Decapoda, Caridea) From Hokkaido, Japan

A little known crangonid, Metacrangon laevis (Yokoya, 1933), is redescribed and illustrated in detail on the basis of specimens recently collected from Hokkaido, Japan. It is distinguishable from close relatives by the absence of paired dorsal carinae on the sixth abdominal somite. Brief notes on the biology are also included.
Stepfamilies from a Legal Perspective

(1998). Stepfamilies from a Legal Perspective. Marriage & Family Review: Vol. 26, No. 3-4, pp. 231-247.
Prediction of elementary school children's socially appropriate and problem behavior from anger reactions at age 4–6 years

Four- to 6-year-olds' anger reactions were observed in preschool/kindergarten and their social functioning was assessed at ages 4-6, 6-8, and 8-10 years. Teachers reported on socially appropriate and social/prosocial behavior, and parents reported on children's problem behaviors. Early anger reactions (especially the use of verbal objections, physical retaliation, and escape behavior) predicted social functioning years later; findings were strongest for teachers' reports of socially appropriate behavior and parents' reports of problem behavior. For aspects of social functioning other than teacher-reported socially appropriate behavior (prosocial/social behavior and low aggression and disruptive behavior), these relations were not due solely to the effects of social skills at age 4-6 on both anger reactions and quality of social functioning in elementary school. Findings were consistent with the possibility that level of social skills at age 4-6 partially mediated the effects of anger reactions on subsequent teacher-reported socially appropriate behavior.
Decreased Cyclic AMP Degradation in NG 108‐15 Neuroblastoma × Glioma Hybrid Cells and S49 Lymphoma Cells Chronically Treated with Drugs that Inhibit Adenylate Cyclase

The increase in hormone-stimulated cyclic AMP accumulation observed in a variety of intact cells after chronic pretreatment with drugs that inhibit adenylate cyclase activity has been attributed to an increase in adenylate cyclase activity following withdrawal of the inhibitory drug. In NG 108-15 mouse neuroblastoma X rat glioma hybrid cells (NG cells) chronically treated with the muscarinic cholinergic agonist carbachol, we have found a significant decrease in the apparent degradation rate constant for cyclic AMP, in addition to an increase in the prostaglandin E1 (PGE1)-stimulated cyclic AMP synthesis rate in intact cells. In carbachol-pretreated NG cells that were stimulated with a maximally effective dose of PGE1, and that accumulated steady-state cyclic AMP concentrations fourfold or more higher than in control cells, the apparent rate constant for degradation was about 53% lower than the value for control cells. In carbachol-pretreated cells stimulated with a submaximal dose of PGE1 to yield a steady-state cyclic AMP concentration comparable to control cells, the apparent rate constant was 31% lower than the value for control cells. In S49 mouse lymphoma cells (S49 cells) chronically treated with an analog of the inhibitory agonist somatostatin, the first-order rate constant for cyclic AMP degradation in intact cells following isoproterenol stimulation was 29% lower than the value for control cells. Despite these changes in the kinetics of cyclic AMP degradation in intact NG cells and S49 cells, there was either no change or a minimal change (less than 10%) in phosphodiesterase activities assayed in extracts of cells chronically exposed to inhibitory drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Power penalty measurement and frequency chirp extraction in silicon microdisk resonator modulators

We demonstrate 5Gbs and10Gbs error free operation of silicon photonic microdisk resonant modulators to a distance of 70km, measure dispersion power penalties and compare the experimental results with theoretically derived values.
A digital analysis of sunspot areas

Full-disk white light images of the Sun have been digitized, calibrated, and examined to determine objective sunspot areas for the early part of the operation of the Solar Maximum Mission satellite. We find that published sunspot areas determined from synoptic programs compare favorably with our digital areas. The mean residual between published areas and our digital areas is approximately 80 millionths of a hemisphere. The largest residual found is 642 millionths on April 1980 for Hale No. 16752.
Localization of gene for familial hypertrophic cardiomyopathy to chromosome 14q1 in a diverse US population.

BACKGROUNDFamilial hypertrophic cardiomyopathy, an inherited primary cardiac abnormality characterized by ventricular hypertrophy, is the leading cause of sudden death in the young. Recent application of restriction fragment length polymorphism markers has provided provocative results, with localization to chromosome 18 (Japanese studies), 16 (Italian studies), 14 (US and French-Canadian studies), and two (National Institutes of Health studies) indicating genetic heterogeneity. Interpretation remains speculative until at least one of these loci is confirmed in unrelated pedigrees by independent investigators.METHODS AND RESULTSWe studied eight unrelated families of varied ethnic origins across the United States. DNA from each individual was digested with restriction enzymes TaqI or BamHI and analyzed by Southern blots followed by hybridization with probes T cell receptor alpha (TCRA), myosin heavy chain beta, D14S25, and D14S26. Multipoint linkage analysis showed a maximum lod score of 4.3, placing the lo...
The mental wormhole: internal attention shifts without regard for distance.

Attention operates perceptually on items in the environment, and internally on objects in visuospatial working memory. In the present study, we investigated whether spatial and temporal constraints affecting endogenous perceptual attention extend to internal attention. A retro-cue paradigm in which a cue is presented beyond the range of iconic memory and after stimulus encoding was used to manipulate shifts of internal attention. Participants’ memories were tested for colored circles (Experiments 1, 2, 3a, 4) or for novel shapes (Experiment 3b) and their locations within an array. In these experiments, the time to shift internal attention (Experiments 1 and 3) and the eccentricity of encoded objects (Experiments 2–4) were manipulated. Our data showed that, unlike endogenous perceptual attention, internal shifts of attention are not modulated by stimulus eccentricity. Across several timing parameters and stimuli, we found that shifts of internal attention require a minimum quantal amount of time regardless of the object eccentricity at encoding. Our findings are consistent with the view that internal attention operates on objects whose spatial information is represented in relative terms. Although endogenous perceptual attention abides by the laws of space and time, internal attention can shift across spatial representations without regard for physical distance.
Simulations on the Theil-Sen regression estimator with right-censored data

This note compares the small-sample efficiency of the extended Theil-Sen estimator to the modified Buckley-James estimator when the predictor is random. Included are situations where the error term is heteroscedastic. In terms of their standard errors, the extended Theil-Sen estimator is found to offer a substantial advantage in various situations, while the modified Buckley-James estimator never offers an advantage when there is 20% or 50% censoring.
Toward Closing the Loop: An Update on Insulin Pumps and Continuous Glucose Monitoring Systems

This article reviews current pump and continuous glucose monitoring therapy and what will be required to integrate these systems into closed-loop control. Issues with sensor accuracy, lag time, and calibration are discussed as well as issues with insulin pharmacodynamics, which result in a delayed onset of insulin action in a closed-loop system. A stepwise approach to closed-loop therapy is anticipated, where the first systems will suspend insulin delivery based on actual or predicted hypoglycemia. Subsequent systems may control to range, limiting the time spent in hyperglycemia by mitigating the effects of a missed food bolus or underestimate of consumed carbohydrates, while minimizing the risk of hypoglycemia.
Non-target effects of neonicotinoid seed treatments; mortality of coccinellid larvae related to zoophytophagy

Abstract Third and fourth instar Harmonia axyridis Pallas larvae feed directly on corn seedlings; therefore they may be at risk if the seedlings are chemically treated. Neonicotinoids are broad-spectrum systemic insecticides that are frequently applied to corn seeds prior to planting to protect seedlings from early-season root and leaf-feeding. In this study, H. axyridis larvae were exposed for 360 min to corn seedlings that had been grown from seeds treated with either thiamethoxam or clothianidin. Neurotoxic symptoms (trembling, paralysis, and loss of coordination) were observed in 72% of the H. axyridis larvae; recovery following neurotoxic symptoms rarely occurred (7%). Starvation of larvae for 48 h prior to seedling exposure may increase tissue consumption; however, there was no difference in the number of starved or satiated larvae that displayed neurotoxic symptoms and died. Neurotoxic symptoms and larval mortality were significantly more likely to occur if larvae were exposed to seedlings grown from seeds treated with neonicotinoids compared to the control. In addition, clothianidin resulted in significantly greater larval mortality (80%) compared to thiamethoxam (53%). Symptoms and mortality were rarely observed if seedlings were not treated with a neonicotinoid seed treatment (3% and 3%, respectively). Coccinellids are abundant in agroecosystems in which neonicotinoid seed treatments are likely to be applied. Therefore, the use of neonicotinoids may have negative effects on these non-target species if early-season leaf-feeding occurs in the field.
Pathological changes in yearly protocol liver biopsy specimens from healthy pediatric liver recipients

Many centers perform biopsies on transplanted livers annually to assess allograft function because serum biochemical tests do not always correlate with histological findings. Although criteria exist for diagnosing acute cellular rejection, no similar criteria exist to describe the histopathological changes observed in the "normal" liver of an immunosuppressed but healthy child. The purpose of this study was to define the histopathological changes in the allografted livers of healthy children who have undergone transplantation and to evaluate them during long-term follow-up. One hundred fifty-eight yearly protocol liver biopsy specimens of 54 children who received transplants between January 1988 and March 1996 and at least 1 year of follow-up were reviewed, and the biopsy findings were correlated with those of serum tests of liver function performed concomitantly. Thirty-three biopsy specimens were excluded because serum transaminase levels were abnormal, the biopsy specimen was abnormal and diagnostic for a specific lesion, or follow-up showed progression of a specific disease process. In addition, time zero biopsy specimens from 21 of the 54 children were available for comparison. In the protocol biopsy specimens, portal and/or parenchymal mononuclear inflammatory infiltrates were frequent findings (48% and 25%, respectively). Other less common features were mild fibrosis (8%) and focal pericholangitis (6%). Findings in both protocol and time zero biopsy specimens included minimal to mild bile ductular proliferation (15% and 9.5%, respectively) and rare hepatocyte necrosis (1.6% and 5%). No yearly protocol biopsy specimens resulted in any patient benefit. Transplanted livers in immunosuppressed children who are clinically healthy and have normal transaminase levels commonly show histological changes consisting of scattered, mild to moderate, portal and/or parenchymal mononuclear infiltrates that are clinically insignificant. Yearly protocol biopsies in healthy pediatric recipients have been abandoned by the investigators after 3 years of follow-up.
From Hypertension to Heart Failure

The prevalence of heart failure is increasing in modern societies. Hypertension is a major contributor to the development of heart failure, whether through the development of left ventricular hypertrophy and diastolic dysfunction or by promoting atherosclerosis and myocardial infarction, which eventually leads to systolic dysfunction and left ventricular dysfunction. Effective therapy for hypertension can prevent more than 50% of heart failure events. Most studies done in the last three decades have used β blockers with diuretics as the modality of therapy. These agents have been shown to effectively prevent the development of heart failure. More recent comparative studies have shown that use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are also effective in preventing heart failure. Calcium channel blockers, however, seem to be less effective in preventing development of heart failure in patients with hypertension. It needs to be emphasized that the most important variable in preventing heart failure is the appropriate treatment of hypertension.
Regulation of SulA cleavage by Lon protease by the C-terminal amino acid of SulA, histidine.

SulA protein, a cell division inhibitor in Escherichia coli , is degraded by Lon protease. The C-terminal eight residues of SulA have been shown to be recognized by Lon; however, it remains to be elucidated which amino acid in the C-terminus of SulA is critical for the recognition of SulA by Lon. To clarify this point, we constructed mutants of SulA with changes in the C-terminal residues, and examined the accumulation and stability of the resulting mutant SulA proteins in vivo . Substitution of the extreme C-terminal histidine residue with another amino acid led to marked accumulation and high stability of SulA in lon + cells. A SulA mutant in which the C-terminal eight residues were deleted (SulAC161) showed high accumulation and stability, but the addition of histidine to the C-terminus of SulAC161 (SulAC161+H) made it labile. Similarly, SulAC161+H fused to maltose-binding protein (MBP–SulAC161+H) formed a tight complex with and was degraded rapidly by Lon in vitro . Histidine competitively inhibited the degradation of MBP–SulA by Lon, while other amino acids did not. These results suggest that the histidine residue at the extreme C-terminus of SulA is recognized specifically by Lon, leading to a high-affinity interaction between SulA and Lon.
On a nonlinear singular diffusion problem:existence and uniqueness

The singular diffusion equation ut=(u−1ux)x:arises in many areas of application, e.g. in the central limit approximation to Carleman's model of Boltzman equation, or, in the expansion of a thermalized electron cloud in plasma physics. This paper concerns the existence and uniqueness of solution of a mixed boundary value problem of equation ut=(um=1ux)x for −1 < m ≤0.
Educating electrical engineers to exploit science

Are the future electrical engineers being trained broadly enough in the sciences? This question has been given serious study at the Massachusetts Institute of Technology, with the result that major changes have been made in the undergraduate electrical curriculum, so as to better equip the students with technical substance and professional vision.
An experimental study of the placebo response under three different situations of pain

Abstract The placebo response was studied in fifty-two obstetrical patients under three different conditions of pain: labor pain, postpartum pain and experimental, ischemic muscle pain. Control subjects were used to evaluate the natural course and spontaneous, non-placebo changes in pain. Pain relief or increase was scored on an equal interval scale from subjective estimations made by the subjects at different times after administration of the placebo. Placebo reactors were arbitrarily defined as individuals showing a response to a placebo greater than one standard deviation above the mean pain relief observed in the control group. Statistical analysis revealed that the number of consistent placebo reactors was not greater than would be expected by chance. The obstetrical patients responded to each placebo situation independently and showed no statistically significant tendency to respond in a consistent way to all three situations. This conclusion is not dependent upon the arbitrary definition of placebo reactor as shown by other statistical tests. Although fundamental and enduring personality characteristics will effect an individual's responsiveness to a placebo or a drug, this study places doubt on the belief that such traits are sufficiently influential to produce placebo responses consistently under different situations. Since general and consistent placebo reactivity was not shown in the current study, basic personality characteristics probably are not prepotent in determining an individual's response to placebos. Predispositions which are ephemeral and which interact with specific therapeutic situations are more likely to be influential in determining a placebo response.
Nonlinear Rescaling as Interior Quadratic Prox Method in Convex Optimization

A class ? of strictly concave and twice continuously differentiable functions ?: R ? R with particular properties is used for constraint transformation in the framework of a Nonlinear Rescaling (NR) method with "dynamic" scaling parameter updates. We show that the NR method is equivalent to the Interior Quadratic Prox method for the dual problem in a rescaled dual space. The equivalence is used to prove convergence and to estimate the rate of convergence of the NR method and its dual equivalent under very mild assumptions on the input data for a wide class ? of constraint transformations. It is also used to estimate the rate of convergence under strict complementarity and under the standard second order optimality condition. We proved that for any ? ? ?, which corresponds to a well-defined dual kernel ? = ??*, the NR method applied to LP generates a quadratically convergent dual sequence if the dual LP has a unique solution.
Autophagy is a critical mechanism for the induction of the antileukemic effects of arsenic trioxide

Arsenic trioxide (As2O3) exhibits potent antitumor effects in vitro and in vivo, but the precise mechanisms by which it generates such responses are not well understood. We provide evidence that As2O3 is a potent inducer of autophagy in leukemia cells. Such induction of autophagy by As2O3 appears to require activation of the MEK/ERK pathway but not the AKT/mammalian target of rapamycin or JNK pathways. In efforts to understand the functional relevance of arsenic-induced autophagy, we found that pharmacological inhibitors of autophagy or molecular targeting of beclin 1 or Atg7 results in reversal of the suppressive effects of As2O3 on leukemic cell lines and primary leukemic progenitors from acute myelogenous leukemia patients. Altogether, our data provide direct evidence that autophagic cell death is critical for the generation of the effects of As2O3 on acute myelogenous leukemia cells and raise the potential of modulation of elements of the autophagic machinery as an approach to enhance the antitumor properties of As2O3 and possibly other heavy metal derivatives.
Structural Determinants of Nicotinic Acid Adenine Dinucleotide Phosphate Important for Its Calcium-mobilizing Activity

Nicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes Ca2+ through a mechanism totally independent of cyclic ADP-ribose or inositol trisphosphate. The structural determinants important for its Ca2+ release activity were investigated using a series of analogs. It is shown that changing the 3-carboxyl group of the nicotinic acid (NA) moiety in NAADP to either an uncharged carbinol or from the 3-position to the 4-position of the pyridine ring totally eliminates the Ca2+release activity. Conversion of the 3-carboxyl to other negatively charged groups, either 3-sulfonate, 3-acetate, or 3-quinoline carboxylate, retains the Ca2+ release activity, although their half-maximal effective concentrations (EC50) are 100–200-fold higher. Changing the 6-amino group of the adenine to a hydroxyl group results in more than a 1000-fold decrease in the Ca2+ release activity. Conversion of the 2′-phosphate to 2′,3′-cyclic phosphate or 3′-phosphate likewise increases the EC50 by about 5- and 20-fold, respectively. Similar to NAADP, all of the active analogs can also desensitize the Ca2+ release mechanism at subthreshold concentrations, suggesting that this novel property is intrinsic to the release mechanism. The series of analogs used was produced by using ADP-ribosyl cyclase to catalyze the exchange of the nicotinamide group of various analogs of NADP with various analogs of NA. An important determinant in NA that is crucial to the base exchange reaction was shown to be the 2-position of the pyridine ring. Neither pyridine-2-carboxylate nor 2-methyl-NA support the exchange reaction. The negative charge and the position of the 3-carboxyl group are nonessential since both pyridine-3-carbinol and pyridine-4-carboxylate support the base exchange reaction. In addition to the information on the structure-activity relationships of NAADP and NA, this study also demonstrates the utility of the base exchange reaction as a general approach for synthesizing NAADP analogs.
Comparison of CNS penetration, tissue distribution, and pharmacology of VP 16-213 by intracarotid and intravenous administration in dogs

AbstractEight beagle dogs received [3H]VP 16–213 at 2 mg/kg administered intravenously (IV) or intra-arterially (IC) through a catheter inserted into the internal carotid artery. Blood, urine, bile, and cerebrospinal fluid (CSF) samples were collected at intervals. At 1, 6, 24 hr, and 2 weeks after drug administration the dogs were sacrificed and the major organs analyzed for drug concentration. VP 16–213 concentration was determined by radiochemical assay and high pressure liquid chromatography. The plasma t1/2 in the IC group of dogs was 1.0 hr, the volume of distribution was I.7 L/kg and the clearance was 1.5 ml/hr/kg. In the IV group the values were 1.7, 3.9, and 1.6, respectively. The CSF concentration peaked at I hr by both routes, but was higher at all time points in the IC group. At 24 hr and 2 weeks after IC VP 16–213, drug concentration in brain tissue was at least four times higher in the IC group compared with the IV group. In extracranial organs the reverse was true, with the bone marrow cell...
Views on Four Key Questions About Zebrafish Research

Our 2004 ‘‘Experts Speak’’ commentary included a series of well-considered perspectives on the potential contributions of the zebrafish to biology and human health. It is fun to look back on those comments. Since that time, the use of morpholino knockdowns as a reverse genetic tool has become commonplace. Insertional mutagenesis with evolving retroviral and now, transposon-based tools, has made it much easier to clone genes found in mutant screens, though the relative strength of ENU mutagenesis to detect phenotypically interesting mutations in essential genes remains. To challenge the ease of morpholino knock-downs in zebrafish, somatic cell knockdowns of mammalian cell culture cells with RNAi has now become commonplace. Broadly-applicable targeted engineering of animal genomes, including zebrafish, looms tantalizingly on the horizon. Before Steve Ekker0s arrival as our new editor, to take another ‘‘snap shot’’ of our moving field, I was asked to help find out what some senior members of the zebrafish community think aboutwhereweare, focusing on four questions (and a ‘‘grab bag’’of questions). Most striking was the large increase in discussion of relevance of the zebrafish to humans, which validates past and future NIH support for zebrafish research. The answers we received are presented in alphabetical order by investigator last name, with editorial changes in brackets. May these comments inspire an everclearer vision of how the zebrafish will contribute to our understanding of the living world.
Normal fluoride content of seawater

Abstract Fluoride concentrations were determined in 224 seawater samples from the Atlantic and Pacific Oceans and from the Caribbean Sea. The most probable value for the mean F/CI ratio (× 1054) in normal seawater was 6·75 with an overall uncertainty of ± 0.03 (based on three times the standard deviation of the mean). The ratio was invariant with respect to geographical location, depth, and water mass. An upper limit was established for its normal variability in seawater, thus allowing more sensitive identification of waters containing anomalous amounts of fluoride. The extra fluoride that has been found in anomalous seawater may be chemically complexed or in acid-soluble colloidal form. Several techniques to discriminate between these possibilities are discussed.
The induction of hapten-specific T cell tolerance using hapten-modified lymphoid membranes. II. Relative roles of suppressor T cells and clone inhibition in the tolerant state.

The cellular nature and specificity of suppressor cells and the mechanisms of tolerance to 2,4-dinitrophenyl-l-fluorobenzene (DNFB) in mice was investigated. Mice tolerized with hapten-modified self membrane, i.e. dinitrophenylated spleen cells (DNP-SC), generated suppressor cells as shown by their ability to transfer unresponsiveness to normal animals. Such suppressor cells were specific for DNFB as they did not interfere with sensitization of normal animals with 2,4,6-trinitro-1-chlorobenzene (picryl chloride). These suppressor cells were of the thymus-derived lymphocyte (T cell) lineage as (a) their activity was abolished by treatment with anti-Θ serum plus complement, and (b) these cells could not be raised in T cell-deprived mice. Kinetic studies of the development of tolerance showed discrepancies between the rate of induction of unresponsiveness in the donor (“phenotypic” tolerance) and the ability to transfer tolerance. One day after receiving 5 × 10 DNP-SC mice were phenotypically tolerant but could not serve as the donors of suppressor cells. 7 days after tolerization with DNP-SC mice were still fully tolerant and also contained suppressor cells, which were no longer demonstrable 14 days after tolerization when mice were still phenotypically tolerant. The ability to transfer tolerance was eliminated by pretreatment with cyclophosphamide (Cy). We postulate that two independent mechanisms of tolerance occur after tolerization with DNP-SC - the rapid induction of clone inhibition and the slower, transient induction of suppressor T cells. Cy had no effect on clone inhibition but eliminated the precursors of suppressor T cells.
Atrial fibrillation produced by prolonged rapid atrial pacing is associated with heterogeneous changes in atrial sympathetic innervation.

Background—Structural and electrophysiological changes of the atria occur with prolonged rapid rates; however, the effects of sustained atrial fibrillation (AF) on autonomic innervation of the atria are unknown. We hypothesized that electrophysiological remodeling from rapid atrial rates is accompanied by altered atrial autonomic innervation. Methods and Results—Six dogs (paced group) underwent atrial pacing at 600 bpm; 9 dogs (control animals) were not paced. All paced dogs developed sustained AF by week 4 of pacing. All 15 animals underwent positron emission tomography imaging of the atria with [C-11] hydroxyephedrine (HED) to label sympathetic nerve terminals. HED retention in the atria was significantly greater in paced dogs compared with control animals (P=0.03). Tissue samples from the atrial appendages had a greater concentration of norepinephrine in paced animals than in control animals (P=0.01). The coefficient of variation of HED retention was also greater in paced animals (P=0.05) and was great...