cssi/SciSciGPT-SciSciNet huggingface dataset:
Pseudomonas aeruginosa AlgR Regulates Type IV Pilus Biosynthesis by Activating Transcription of the fimU-pilVWXY1Y2E Operon

The response regulator AlgR is required for Pseudomonas aeruginosa type IV pilus-dependent twitching motility, a flagellum-independent mode of solid surface translocation. Prior work showed that AlgR is phosphorylated at aspartate 54, and cells expressing an AlgR variant that cannot undergo phosphorylation (AlgRD54N) lack twitching motility. However, the mechanism by which AlgR controls twitching motility is not completely understood. We hypothesized that AlgR functioned by activating genes within the prepilin fimU-pilVWXY1Y2E cluster that are necessary for type IV pilin biogenesis. Reverse transcriptase PCR analysis showed that the fimU-pilVWXY1Y2E genes are cotranscribed in an operon, which is under the control of AlgR. This supports prior transcriptional profiling studies of wild-type strains and algR mutants. Moreover, expression of the fimU-pilVWXY1Y2E operon was reduced in strains expressing AlgRD54N. DNase footprinting and electrophoretic mobility shift assays demonstrate that AlgR but not AlgRD54N bound with high affinity to two sites upstream of the fimU-pilVWXY1Y2E operon. Altogether, our findings indicate that AlgR is essential for proper pilin localization and that phosphorylation of AlgR results in direct activation of the fimU-pilVWXY1Y2E operon, which is required for the assembly and export of a functional type IV pilus.
Quo vadimus? — Much hard work is still needed

Physical aspects of computation that just a few years ago appeared tentative and tenuous, such as energy recycling in computation and quantum computation, have now grown into full-fledged scientific businesses. Conversely, concepts born within physics, such as entropy and phase transitions, are now fully at home in computational contexts quite unrelated to physics. Countless symposia cannot exhaust the wealth of research that is turning up in these areas. The “Physics of Computation” workshops cannot and should not try to be an exhaustive forum for these more mature areas. I think it would be to everyone's advantage if the workshops tried to play a more specialized and more critical role; namely, to venture into uncharted territories and to do so with a sense of purpose and of direction. Here I briefly suggest a few possibilities; among these, the need to construct a general, model-independent concept of “amount of computation”, much as we already have one for “amount of information”. I suspect that, much as the inspiration and prototype for the latter was found in physical entropy, so the inspiration and prototype for the former will be found in physical action.
Templated Platinum/Carbon Oxygen Reduction Fuel Cell Electrocatalysts

This paper describes a new class of templated electrocatalysts for oxygen reduction in polymer electrolyte membrane fuel cells. Electrocatalysts were made by two consecutive procedures. First, porous silica particles were formed by sol−gel synthesis conducted in the aqueous phase of a dispersed system of surfactant micelles and oil microemulsion droplets. This oxide material with bimodal pore size distribution (biporous silica) was then templated by infiltration with solutions of carbon precursor (sucrose) and platinum salt, followed by controlled pyrolysis and dissolution of the silica template. The effect of the bimodal porous structure of the sacrificial silica particles on the structure and oxygen reduction performance of platinum electrocatalysts is discussed. Morphology, composition, and structure of templated carbon support and decorated platinum nanophase were studied through extensive characterization by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), X-ray diffract...
Effects of N-acetylcysteine on renal dysfunction in neonates undergoing the arterial switch operation

Objective We evaluated N-acetylcysteine, a potent antioxidant, as prevention for renal dysfunction in infants undergoing cardiac surgery for dextro-transposition of the great arteries. Methods Twenty-one neonates undergoing the arterial switch operation were randomized to receive either placebo or intravenous N-acetylcysteine. Serial data were collected on fluid balance, serum creatinine, inotropic support, cardiac output, and length of stay. Results Hospital and 30-day survival was 100%. No serious adverse events were attributable to the drug. Subjects treated with N-acetylcysteine had a higher urine output at 24 hours (175 mL vs 96 mL; P Conclusions In this pilot study, perioperative treatment with N-acetylcysteine resulted in improved urine output, shorter time to negative fluid balance, and attenuation of the rise in creatinine. These effects of N-acetylcysteine may translate to improved outcomes for infants undergoing complex cardiac operations.
Phosphatidylcholine-specific phospholipase C and D in stimulation of RAW264.7 mouse macrophage-like cells by lipopolysaccharide.

Abstract The purpose of these studies was to identify the role of phospholipases in the activation of macrophages by lipopolysaccharide (LPS). Tricyclodecan-9-yl-xanthogenate (D609), an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC); butanol, an inhibitor of phosphatidylcholine phospholipase D (PC-PLD); and propranolol, an inhibitor of phosphatidate phosphohydrolase, were used in the study. Treatment of RAW264.7 murine macrophage-like cells with LPS resulted in expression of inducible nitric oxide synthase and tumor necrosis factor-α. The expression was partially inhibited by D609, butanol, or propranolol and was completely blocked by the combination of D609 and butanol. RAW264.7 cells constitutively produced low basal levels of diacylglycerol and phosphatidic acid; production of both was significantly increased after stimulation with LPS, reaching a peak in 2–3 min and remaining elevated after 30 min. In LPS-induced RAW264.7 cells, diacylglycerol was suppressed by each of the three inhibitors alone and almost abolished by D609 plus butanol or D609 plus propranolol. Phosphatidic acid was reduced to basal level by butanol after LPS stimulation for 2.5 min and by butanol plus D609 after LPS stimulation for 2.5 or 10 min. Taken together, these data indicate that activation of RAW264.7 cells by LPS can be mediated by the activities of both PC-PLC and PC-PLD.
Search for fractional charges using droplet-jet techniques.

We report the results of a search for fractional electric charges in stable matter. We obtain 90%-C.L. upper limits upon the concentration of fractional charges in the sample tetraethylene glycol examined of 1 per 64 ..mu..g for +0.33e and/or +0.66e fractional charges, and 1 per 28 ..mu..g for +0.33e and/or -0.66e fractional charges. Our method employed so-called ''satellite'' droplets formed in the breakup of a liquid jet. The droplets were shot vertically downward and charge-analyzed using a horizontal electric field. The final positions, reflecting a charge sensitivity of up to 1.8 mm per electron charge, were measured with a laser-scanner-based detector. Our charge resolution was better than (1/30 of an electron charge.
On separating space and time variations of auroral precipitation: Dual DMSP-F6 and -F8 observations

Abstract After the launch of DMSP-F8, into an almost identical orbit to DMSP-F6, there occurred periods every approximately 11 days when the two satellites were very close to each other, thereby allowing for distinguishing between temporal and spatial effects on measured auroral precipitation. We present observations of one such period, when we were able to resolve space and time through multi-point measurements. In this period, the DMSP satellites observed the same general auroral zone precipitation pattern. However one large-scale feature changed vastly in the two minute time separation between the satellites. We demonstrate how this feature can be identified and mapped using two low altitude satellites together with ground magnetic field and radar data. This example underscores the utility of “clustered” satellite constellations at low earth orbit for auroral observations.
Action of neomycin on the metabolism of polyphosphoinositides in the guinea pig kidney.

(Received 8 August 1976; accepted 4 February 1977) Abstract-The effect of neomycin on the metabolism of phospholipids was investigated in the guinea pig kidney both in uivo and in vitro. In ho, after an intraperitoneal injection of (32P)orthophosphate, the polyphosphoinositides (phosphatidylinositol phosphate and phosphatidylinositol diphosphate) were the most rapidly labeled phospholipids reaching maximal radioactivity within 40min. The labeling of these lipids paralleled that of the nucleotide phosphate pool. After chronic treatment of animals with neomycin (lOOmg/kg body weight daily for 6 days), phosphate incorporation into the polyphos- phoinositides was decreased whereas incorporation into other lipids remained unaffected. Also, the amount of phosphatidylinositol diphosphate was reduced from 270 to 170 nmoles/g of kidney. No significant changes in phospholipid labeling were found in the liver. Experiments in vitro with kidney homogenates demonstrated inhibition of labeling of phosphatidylinositol diphosphate from (Y-~')ATP and inhibition of the enzymatic hydrolysis of previously labeled (32P)phosphatidylinositol phosphate and diphosphate in the presence of neomycin. A direct antibiotic-lipid interaction is dis- cussed as a mechanism for the observed effects of neomycin on renal polyphosphoinositide metabolism.
Hydrodynamic studies on model branched polystyrenes

The measurement of the sedimentation velocity coefficient of narrow distribution linear, four-arm and six-arm star and comb polystyrenes in a theta solvent permits the experimental determination of h, i.e., the ratio of the translational friction coefficients of the branched polymer to that of its linear homolog. A comparison of experimental h/g1/2 values with theoretical predictions can then be made. It was observed that the equivalent hydrodynamic radii derived from sedimentation and intrinsic viscosity measurements are identical within experimental error.
The effect of normal aging on the coupling of neural activity to the bold hemodynamic response.

The use of functional neuroimaging to test hypotheses regarding age-related changes in the neural substrates of cognitive processes relies on assumptions regarding the coupling of neural activity to neuroimaging signal. Differences in neuroimaging signal response between young and elderly subjects can be mapped directly to differences in neural response only if such coupling does not change with age. Here we examined spatial and temporal characteristics of the BOLD fMRI hemodynamic response in primary sensorimotor cortex in young and elderly subjects during the performance of a simple reaction time task. We found that 75% of elderly subjects (n = 20) exhibited a detectable voxel-wise relationship with the behavioral paradigm in this region as compared to 100% young subjects (n = 32). The median number of suprathreshold voxels in the young subjects was greater than four times that of the elderly subjects. Young subjects had a slightly greater signal:noise per voxel than the elderly subjects that was attributed to a greater level of noise per voxel in the elderly subjects. The evidence did not support the idea that the greater head motion observed in the elderly was the cause of this greater voxel-wise noise. There were no significant differences between groups in either the shape of the hemodynamic response or in its the within-group variability, although the former evidenced a near significant trend. The overall finding that some aspects of the hemodynamic coupling between neural activity and BOLD fMRI signal change with age cautions against simple interpretations of the results of imaging studies that compare young and elderly subjects.
JAK/STAT pathway dysregulation in tumors: A Drosophila perspective

Sustained activation of the JAK/STAT pathway is causal to human cancers. This pathway is less complex in Drosophila, and its dysregulation has been linked to several tumor models in this organism. Here, we discuss models of metastatic epithelial and hematopoietic tumors that are causally linked to dysregulation of JAK/STAT signaling in Drosophila. First, we focus on cancer models in imaginal discs where ectopic expression of the JAK/STAT pathway ligand Unpaired downstream of distinct tumor suppressors has emerged as an unexpected mediator of neoplastic transformation. We also discuss the collaboration between STAT and oncogenic Ras in epithelial transformation. Second, we examine hematopoietic tumors, where mutations that cause hyperactive JAK/STAT signaling are necessary and sufficient for “fly leukemia”. We highlight the important contributions that genetic screens in Drosophila have made to understanding the JAK/STAT pathway, its developmental roles, and how its function is co-opted during tumorigenesis.
First study of the negative binomial distribution applied to higher moments of net-charge and net-proton multiplicity distributions

Abstract A study of the first four moments (mean, variance, skewness, and kurtosis) and their products ( κ σ 2 and Sσ) of the net-charge and net-proton distributions in Au + Au collisions at s NN = 7.7 – 200 GeV from HIJING simulations has been carried out. The skewness and kurtosis and the collision volume independent products κ σ 2 and Sσ have been proposed as sensitive probes for identifying the presence of a QCD critical point. A discrete probability distribution that effectively describes the separate positively and negatively charged particle (or proton and anti-proton) multiplicity distributions is the negative binomial (or binomial) distribution (NBD/BD). The NBD/BD has been used to characterize particle production in high-energy particle and nuclear physics. Their application to the higher moments of the net-charge and net-proton distributions is examined. Differences between κ σ 2 and a statistical Poisson assumption of a factor of four (for net-charge) and 40% (for net-protons) can be accounted for by the NBD/BD. This is the first application of the properties of the NBD/BD to describe the behavior of the higher moments of net-charge and net-proton distributions in nucleus–nucleus collisions.
Photoperiodism as a Factor in Feeding Rhythms of Broiler Chickens

Abstract BROILERS exposed to continuous light at a single intensity during the growing period are heavier than those exposed to either varying intensities or intermittent light and dark periods (e.g. Moore, 1957; Shutze et al., 1960; Krueger et al, 1963; Beane et al., 1962, 1965). Observations indicate that under continuous illumination growth is more rapid at low than at higher intensities (Skoglund and Palmer, 1961; Cherry and Barwick, 1962; Beane et al, 1965). The diurnal feeding patterns of broilers have been studied by Siegel and Guhl (1956) and Siegel et al. (1962). They found that the percentage of birds feeding was highest at the beginning and at the end of the daily light period suggesting that the birds have become conditioned to the dark periods. The experiment reported there was designed to determine feeding rhythms, growth, feed efficiency, and endocrine responses of broilers maintained under several light regimes. EXPERIMENTAL PROCEDURE Four . . .
Effect of tethering chemistry of cationic surfactants on clay exfoliation, electrospinning and diameter of PMMA/clay nanocomposite fibers

We examine the influence of tethering chemistry of cationic surfactants on exfoliation of montmorillonite (MMT) clay dispersed in methyl methacrylate (MMA) followed by in-situ polymerization to form poly(methyl methacrylate) (PMMA) nanocomposites, the effect of exfoliation and clay loading on the rheology of polymer/clay dispersions in dimethyl formamide, and the diameters of nanocomposite fibers formed from these dispersions by electrospinning. Incorporation of an additional reactive tethering group of methacryl functionality significantly improves the intercalation and exfoliation of clays in both in-situ polymerized PMMA nanocomposites and the corresponding electrospun fibers. The proper surfactant chemistry also increases the dispersion stability, extensional viscosity, extent of strain hardening and thus the electrospinnablity of the nanocomposite dispersions, especially at low nanocomposite concentrations. The degree of the enhancement in electrospinnability by clays with proper tethering chemistry is at least the same as or greater than that obtained with three times higher loading level of clay particles without proper tethering chemistry in the nanocomposites. These results suggest a new strategy to produce smaller diameter fibers from very dilute polymer solutions, which are otherwise not electrospinnable, by incorporating a small amount of well-exfoliated clays.
Divisibility in O-Primitive Lattice-Ordered Permutation Groups

We show that divisibility fails in a wide spectrum of periodic lattice-ordered permutation groups. The methods are applied to the six previously known ‘pathological’ doubly transitive groups represented on ℝ or on ℝ+, and only two of these groups turn out to be divisible.
Risk of colorectal adenoma and carcinoma after colectomy for colorectal cancer in patients meeting Amsterdam criteria.

Objective: To report the risk of metachronous colorectal neoplasia after colectomy for cancer in Hereditary Nonpolyposis Colorectal Cancer (HNPCC) syndrome. Summary background data: Patients meeting Amsterdam criteria for diagnosis of HNPCC have a lifetime colorectal cancer risk approaching 80%, and a metachronous cancer rate of approximately 25%. Therefore, when colon cancer is diagnosed, total rather than segmental colectomy is advocated. However, information about adenoma and carcinoma risk after index surgery is still underreported. Methods: A hereditary colorectal cancer database was reviewed for patients meeting Amsterdam criteria who underwent colectomy for cancer. Patient demographics, surgical management, and results of follow-up were recorded. Metachronous colorectal adenoma and carcinoma development were the primary end points. Results: A total of 296 patients (253 with segmental colectomy and 43 with total colectomy/ileorectal anastomosis) were analyzed. Of the 253 segmental colectomy patients, 221 (88%) had postoperative endoscopic surveillance with median follow-up of 104 months. In 74 patients (33%), 256 adenomas were detected, including 140 high-risk adenomas in 48 patients (22%). Fifty-five patients (25%) developed a second colorectal cancer at a median of 69 months after index surgery. Stages of the metachronous cancers were I-16, II-18, III-12, and IV-2. By comparison, 4 of 38 patients (11%) who underwent total colectomy developed subsequent high-risk adenomas and 3 (8%) developed metachronous cancer. Conclusions: Amsterdam patients undergoing partial colectomy have a high rate of metachronous high-risk adenomas and carcinomas. Total colectomy for the index cancer is the procedure of choice. For either surgical option, yearly endoscopic surveillance is essential to remove premalignant adenomas.
Optimizing High School Curriculum Assignments.

Abstract A quantitative model is described for the optimal assignment of students to courses for their complete high school careers. Values of curriculum, assigned by counselor-judges for types of students, are found to be highly reliable (rtt = 0.65). Model-generated student schedules are found to be unfailing in their conformity to all of the constraints of the test high school's curriculum. ACPP (the Automatic Curriculum Planning Program) incorporates a two-stage dynamic programming algorithm with curricular sequence constraints resolved by Boolean reduction techniques.
Effects of Consumer Preferences for Foreign Sourced Products

When deciding on overseas production locations, the manager must take into account not only resource and cost benefits, but the effect that country of origin may have on consumer evaluations. An experiment conducted by a telephone survey procedure examined country of origin perceptions of twelve countries and eight products, using both perceived quality and choice measures. As hypothesized, preferences were found to be more product specific for industrialized than less developed countries. In addition, hypotheses that performance risk and brand moderate the effects of country were upheld under most conditions.
Influence of temperature on grape leafhoppers in southcentral Washington

The 2 most important leafhopper pests of grapes in Washington are the Western grape leafhopper, Erythroneura elegantula Osborn, and Erythroneura ziczac Walsh. The influence of different constant temperatures on the egg and nymphal stages of E. ziczac and on the nymphal stage of E. elegantula was examined. Development times of E. ziczac eggs ranged from 33.1 d at 15 degrees C to 8.6 d at 32.5 degrees C. E. ziczac nymphal development ranged from 40.2 d at 16 degrees C to 11.1 d at 29.5 degrees C. The average number of degree-days required for development from oviposition to imaginal molt was 435.4. This was slightly higher than the previously published value of 390.5 DD for field reared E. ziczac. E. elegantula nymphal development ranged from 38.0 d at 16.0 degrees C to 11.8 d at 32.5 degrees C. The average number of degree-days required for E. elegantula development from eclosion to imaginal molt was 246.3. Constant temperature data for the egg and nymphal stages of E. ziczac and for the nymphal stage of E. elegantula was fitted to a developmental model based on enzyme reaction kinetics. The egg and nymphal stages of E. ziczac fitted the model with r2 values of 0.9992 and 0.9990, respectively. The E. elegantula nymphal stage fitted the model with an r2 value of 0.9996. Lethal freezing temperatures for E. ziczac adults collected on 28 January, 4 February, and 14 November, 1994 were -27.1, -26.3, and -27.2 degrees C, respectively. Freezing temperatures for E. elegantula on the same dates were -24.6, -24.1, and -25.3 degrees C, respectively.
Discoveries missed, discoveries made: creativity, influence, and fame in chemistry

Abstract The paper describes some of the historical background of the discoveries of the diene synthesis and the orbital symmetry conservations rules. It examines the circumstances that prevented these discoveries from being made by earlier investigators and speculates about the mental qualities conductive to creativity in science.
Articulation: brightness, apparent illumination, and contrast ratios

Luminance edges in the environment can be due to regions that differ in reflectance or in illumination. In three experiments, we varied the spatial organization of 10 achromatic (simulated) surfaces so that some arrangements were consistent with an ecologically valid and parsimonious interpretation of 5 surfaces under two different illuminants. A constant contrast-ratio along a luminance edge in the scene allows this interpretation. The brightness of patches in this condition was compared to their brightness with minimally different spatial arrangements that fail to maintain the constant contrast-ratio criterion. When the spatial arrangement of the 10 surfaces included a luminance edge satisfying the constant contrast-ratio criterion, brightness changed systematically, compared to arrangements without such a luminance edge. We account for the results by positing that a luminance edge with a constant contrast-ratio segments the scene into regions of lower and higher illumination, with the same effect as a difference in real physical illumination: all else equal, a given surface appears brighter under higher than under lower illumination.
Factors influencing physician participation in Medicaid in the USA

Physician participation in Medicaid is an important factor in the determination of access to health care for low‐income individuals. This study seeks to provide insight into the factors that affect physicians’ decisions to participate in the Medicaid program. As Medicaid is administered under broad federal guidelines, there is some degree of commonality between the different programs in each state and many physician and market unique factors traverse state lines. On this basis, several propositions are presented. Physician participation in Medicaid is posited to be positively associated with Medicaid reimbursement rates, the percentage of the available patient base in the Medicaid program, physician perceived autonomy and whether the physician is a foreign medical graduate. Alternately, participation decisions are proposed to be negatively associated with practice costs, competition for paying patients, the difference between the marginal revenue derived from paying patients and revenue from Medicaid patients, and board certification. This study seeks to provide a deeper understanding of the effects of changes to the Medicaid program, and suggests their likelihood of success in providing care to vulnerable populations.
Personalizing Cancer Care: American Society of Clinical Oncology Presidential Address 2009

I would like to welcome you all to Orlando, FL, and the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting. This has been a challenging year for people everywhere due to the global economic recession and the resulting unemployment and loss of health care benefits. But it has also been a year of great hope for a new administration in Washington, DC, that is very supportive of biomedical research and committed to curing cancer. I am pleased to see so many of you gathered here to share our common goal to improve the outcomes of cancer patients through research and the delivery of high-quality care. The next few days will present an extraordinary array of educational sessions and scientific presentations that focus on our vision to deliver the right care to the right person at the right time. We hear much today about “personalized medicine.” Thus, as the theme of this year’s Annual Meeting, I have chosen “Personalizing Cancer Care,” and you will see it, in its many dimensions, in every session of the Meeting. Personalization is the new buzzword in health care and health policy— but what does it mean for cancer patients and oncologists? For the next few minutes, I’ll share with you what I think this means for our community, why it’s important, and how ASCO members can bring this concept to life for our patients.
Stimulus class formation and concept learning: establishment of within- and between-set generalization and transitive relationships via conditional discrimination procedures.

Three students with moderate mental retardation were taught a complex stimulus class with a two-choice conditional discrimination procedure applied across eight 10-member stimulus sets. Each set was composed of five age-appropriate and five age-inappropriate examples of clothing, accessories, and leisure items (e.g., a Walkman radio). Discrimination training was programmed serially across each set, and generalization probes were conducted concurrently among all sets. Generalization probes consisted of unreinforced conditional matching trials with comparison items being drawn from (a) the set undergoing training (within-set probes), (b) sets not undergoing training (between-set probes), and (c) both sample and comparison items from different sets (transitive stimulus control probes). Results indicate that within-set generalization, between-set generalization, and transitive stimulus relations controlled responding by all 3 students for items that had been contingently associated with reinforcement. However, items that gained control of responding through within-set and between-set generalization alone (i.e., not acquired through contingent reinforcement) remained at baseline levels during transitive stimulus control probes. Results are discussed in terms of a taxonomy of multiple sources of stimulus control that underlie socially defined and maintained stimulus classes.
17O NMR spectroscopy (natural abundance) of heterocycles: Anhydrides

17O NMR spectra were recorded for several series of anhydrides (⩽0.5 M) in dried acetonoitrile at 75°C. The 17O NMR data for simple anhydrides were found to be highly sensitive [acetic anhydride, δ 411 ppm (CO), δ 273; glutaric anhydride (2), δ 396 ppm (CO), δ 288 ppm; succinic anhydride δ 376 (CO), δ 301; maleic anhydride, δ 401 (CO), δ 252; phthalic anhydride (27), δ 374 (CO), δ 263]. The 17O NMR data were found to be sensitive to ring size and conformation. Substitutent effects on a series of maleic anhydrides could be rationalized in terms of electronic effects. In contrast, the 17O NMR data for polycyclic succinic anhydrides showed that the chemical shifts of the carbonyl oxygens were roughly constant, while those of the central oxygens were sensitive to structure. The 17O NMR data for homophthalic anhydride [δ 397 (CO), δ 372 (CO), δ 273] were consistent with those for 2 and 27; the data for pyridine-2,3-dicar-boxylic anhydride [δ 383 (CO), δ 380 (CO), δ 263] could be rationalized in terms of electronic effects, and those for 3,4-dihydronaphthalene-1,2-dicarboxylic anhydride [δ 392 (CO), δ 387 (CO), δ 252] were explained by compressional and electronic effects.
An Enzymatically Active Chimeric HIV-1 Reverse Transcriptase (RT) with the RNase-H Domain of Murine Leukemia Virus RT Exists as a Monomer

The existence of retroviral reverse transcriptases as monomers or dimers is rather intriguing. A classical example of the former is murine leukemia virus reverse transcriptase (MuLV RT), while human immunodeficiency virus type 1 (HIV-1) RT represents the latter. A careful scrutiny of the amino acid sequence alignment of the two enzymes pinpoints the region tentatively responsible for this phenomenon. We report here the construction of a chimeric enzyme containing the first 425 amino acid residues from the N-terminal domain of HIV-1 RT and 200 amino acid residues from the C-terminal domain of MuLV RT. The chimeric enzyme exists as a monomer with intact DNA polymerase and RNase-H functions.
Irreversible enzyme inhibitors. LXXXI. Further observations on the mode of binding of the anilino moiety of 2-amino-5-(anilinopropyl)-6-methyl-4-pyrimidinol to dihydrofolic reductase and thymidylate synthetase

Replacement of phenyl group of 2-amino-5-(anilinopropyl)-6-methyl-4-pyrimidinol (III) by benzyl (XI) led to a large loss in binding to both dihydrofolic reductase and thymidylate synthetase; the binding by XI returned when the protonated benzylamino group was N-acetylated to XII, which removes the charge at pH 7.4 and changes the ground-state conformation of the benzene ring. Replacement of the benzyl group of the acetamide, XII, with the polar 2-, 3-, or 4-, picolyl groups also led to a loss in binding. Substitution of p-fluoro or m-trifluoromethyl on the anilino group of III, or replacement of the anilino of III by 3-pyridylamino, gave little - if any - enhancement in binding to the enzymes.
Use of the Optum Labs Data Warehouse To Assess Test Ordering Patterns for Diagnosis of Helicobacter pylori Infection in the United States

We surveyed national Helicobacter pylori diagnostic testing practices and diagnoses using commercial and Medicare medical claims data from Optum Labs (Cambridge, MA). Serologic testing for antibodies to H. pylori remains the most commonly ordered diagnostic test despite recent expert recommendations. Changes in reimbursement for serologic testing will likely drive future provider ordering practices.
Bypassing the compromised mitochondrial electron transport with methylene blue alleviates efavirenz/isoniazid-induced oxidant stress and mitochondria-mediated cell death in mouse hepatocytes.

Efavirenz (EFV) is an anti-retroviral drug frequently combined with isoniazid (INH) to treat HIV-1/tuberculosis co-infected patients. Both drugs have been associated with idiosyncratic liver injury (DILI), but combined anti-retroviral and anti-tubercular therapy can increase the risk for DILI as compared to either drug class alone. Because both EFV and INH have been implicated in targeting mitochondria, we aimed at exploring whether the two drugs might cause synergistic effects on the electron transport chain. We found that EFV inhibited complex I activity in isolated mouse liver mitochondria (IC50 ˜30 μM), whereas hydrazine, a major metabolite of INH generated by acylamidase-mediated hydrolytic cleavage, inhibited complex II activity (IC50 ˜30 μM). Neither INH alone (≤1000 μM) nor EFV alone (≤30 μM) was able to induce cell injury in cultured mouse hepatocytes. However, combined EFV/INH exposure resulted in increased superoxide formation and peroxynitrite stress, leading to the opening of the cyclosporine A-insensitive mode of the mitochondrial permeability transition (mPT), and necrotic cell death. The peroxynitrite scavengers, CBA or Fe-TMPyP, protected against mPT induction and alleviated cell injury. The acylamidase inhibitor bis-p-nitrophenyl phosphate prevented cell injury, suggesting that hydrazine greatly contributed to the toxicity. Methylene blue, a redox-active alternative electron acceptor/donor that bypasses complex I/II, effectively protected against EFV/INH-induced toxicity. These data demonstrate that, in murine hepatocytes, the mitochondrial electron transport chain is a critical target of combined EFV/INH exposure, and that this drug combination can lead to peroxynitrite stress-induced mPT and hepatocellular necrosis. These results are compatible with the concept that underlying silent mitochondrial dysfunction may be a key susceptibility factor contributing to idiosyncratic drug-induced liver injury.
Causes and consequences of extreme Permo-Triassic warming to globally equable climate and relation to the Permo-Triassic extinction and recovery

Permian waning of the low-latitude Alleghenian/Variscan/Hercynian orogenesis led to a long collisional orogeny gap that cut down the availability of chemically weatherable fresh silicate rock resulting in a high-CO2 atmosphere and global warming. The correspondingly reduced delivery of nutrients to the biosphere caused further increases in CO2 and warming. Melting of polar ice curtailed sinking of O2- and nutrient-rich cold brines while pole-to-equator thermal gradients weakened. Wind shear and associated wind-driven upwelling lessened, further diminishing productivity and carbon burial. As the Earth warmed, dry climates expanded to mid-latitudes, causing latitudinal expansion of the Ferrel circulation cell at the expense of the polar cell. Increased coastal evaporation generated O2- and nutrient-deficient warm saline bottom water (WSBW) and delivered it to a weakly circulating deep ocean. Warm, deep currents delivered ever more heat to high latitudes until polar sinking of cold water was replaced by upwelling WSBW. With the loss of polar sinking, the ocean was rapidly filled with WSBW that became increasingly anoxic and finally euxinic by the end of the Permian. Rapid incursion of WSBW could have produced ∼20 m of thermal expansion of the oceans, generating the well-documented marine transgression that flooded embayments in dry, hot Pangaean mid-latitudes. The flooding further increased WSBW production and anoxia, and brought that anoxic water onto the shelves. Release of CO2 from the Siberian traps and methane from clathrates below the warming ocean bottom sharply enhanced the already strong greenhouse. Increasingly frequent and powerful cyclonic storms mined upwelling high-latitude heat and released it to the atmosphere. That heat, trapped by overlying clouds of its own making, suggests complete breakdown of the dry polar cell. Resulting rapid and intense polar warming caused or contributed to extinction of the remaining latest Permian coal forests that could not migrate any farther poleward because of light limitations. Loss of water stored by the forests led to aquifer drainage, adding another ∼5 m to the transgression. Non-peat-forming vegetation survived at the newly moist poles. Climate feedback from the coal-forest extinction further intensified warmth, contributing to delayed biotic recovery that generally did not begin until mid-Triassic, but appears to have resumed first at high latitudes late in the Early Triassic. Current quantitative models fail to generate high-latitude warmth and so do not produce the chain of events we outline in this paper. Future quantitative modeling addressing factors such as polar cloudiness, increased poleward heat transport by deep water and its upwelling by cyclonic storms, and sustainable mid-latitude sinking of warm brines to promote anoxia, warming, and thermal expansion of deep water may more closely simulate conditions indicated by geological and paleontological data.
Sensing of motion related errors in multiaxis Machines

The aim of this paper is the formulation of the principles for the development of optical measurement systems for the measurement of motion related errors in multiaxis machines. Basic system configurations for rotary and prismatic joints are discussed, and their governing linearized equations derived in explicit analytical form.
Toxicology of selenium: A review

(1980). Toxicology of selenium: A review. Clinical Toxicology: Vol. 17, No. 2, pp. 171-230.
An instrument scheduler design for energy neutral coastal monitoring systems deployment

Advances in computing, communications, and sensor technologies are creating new opportunities to exploit low-cost instrumentation for widespread and long-term environmental observation. Because a tethered energy infrastructure is usually not available at these remote locations, localized energy harvesting and power management must be employed for the perpetual energy-neutral operation at low cost with low maintenance. Our strategy is to schedule instruments wisely to execute the sensing mission during the targeted periodic or sporadic events, and to 'sleep' or turn off whenever else for energy conservation. In this paper we present the design of a programmable instrument scheduler that works with an Arduino for power management based on real time clock (RTC). The instrument scheduler allows the duty cycle of power-intensive sensing components at arbitrary schedules in the Arduino software. The current circuit hardware is capable of switching four power channels, including one for itself. This instrument scheduler has been used in several practical deployments to control an ecological observation platform of video cameras and wireless networking equipment. The erosion monitoring platform was implemented at the Thompson Island (Boston, Massachusetts, USA) in October 2012 and at the Jones River watershed (Kingston, Massachusetts, USA) in September 2013. Both systems have been in operation as designed since installation, and are expected to continue operating indefinitely. The deployed systems demonstrate how duty cycling can achieve substantial energy savings on a diverse set of devices through complete shutdown. This approach is expected to have wide applicability for a variety of environmental and ecological studies.
Germination, Emergence, and Yield of 20 Plant–Color, Seed–Color Near‐Isogenic Lines of Grain Sorghum

Although there is growing demand for sorghum [Sorghum bicolor (L.) Moench] with white seed and tan plant color, there is limited information on the overall agronomic fitness of sorghum with these characters. A set of experiments was conducted to evaluate the combined effects of plant color and seed color on sorghum germination, emergence, and agronomic performance. Twenty near-isogenic lines with red seed/tan plant (RT), red seed/purple plant (RP), white seed/ tan plant (WT), white seed/purple plant (WP) phenotypes were tested under field and laboratory conditions. Plant color x seed color interactions were not significant. Purple plant color phenotypes had higher cold germination, higher germination after accelerated aging, and greater seedling elongation at 10 d than tan plant color phenotypes. Plant color did not influence standard warm germination. No differences in standard warm germination or seed vigor test results were attributable to seed color. Seedling emergence under field conditions was higher for the red seed than the white seed phenotype. Grain yield was higher for the white seed than the red seed phenotype, and higher for the purple plant color than the tan plant color phenotype. Grain test weights from purple plant color lines were higher than those from tan plant color lines. All four phenotypes included relatively high yielding lines. There was considerable overlap between WT, WP, RT, RP lines in yield and other indicators of agronomic performance leading to the conclusion that white seed and tan plant color lines with comparable performance to red seed and purple plant color lines can be selected from segregating breeding populations.
Within-subject memory decline in middle-aged rats: effects of intraseptal tacrine

A longitudinal design was used to examine spatial working memory performance in aging Long-Evans rats on a 12-arm, delayed-non-match-to-sample radial maze task. Compared to performance at 12-13 months of age, the same rats exhibited a significant performance deficit at 15-16 months of age across all retention intervals (1.5-10h). All rats exhibited some degree of decline, and no rat performed as well as they had 3 months earlier. This early onset deficit may relate to the degree of difficulty required to perform accurately in a task that maximizes both spatial information processing and flexible working memory representations. Following our observation, rats were implanted with a chronic cannula aimed at the medial septal nucleus. Acute intraseptal tacrine treatments (0.0-25 micrograms/0.5 microl) did not significantly affect any index of performance. Rats exhibited further memory decline over the course of testing (up to 20 months of age). Detection of early onset dysfunction could allow for experimental analysis of underlying mechanisms and therapeutic strategies early in the course of age-related changes.
Touching In Biological Systems: A 3D Force Microscope

We are creating a microscopy system that allows a scientist to be an interactive actor in biological systems. Scanning probe microscopy (SPM) is being applied in a wide range of problems in biology, including the imaging of cell membranes and single molecules, and the measurement of the forces that bind ligands and maintain molecular conformations. Over the past decade we have developed user interfaces for SPM that allow the scientist to be an actor in the experiment. By moving a pen in held in hand, the user can control the motion of the probe tip on the surface, and through the force display capabilities of the pen, feel the surface and the biological sample. Applications of this interface include viruses, fibrin and nanotubes. However, performing force measurements inside cells and other biological systems remains a difficult challenge. The SPM tip, due to its overall dimensions, will strongly perturb a biological system such as a live cell or the extracellular matrix. The trick to solving this dilemma is to free the tip of the SPM probe from the cantilever. We have developed a 3D force microscope by manipulating a freely suspended bead in liquid. By holding a pen in hand, the user can control the forces applied to and the resulting motion of a bead suspended in a biological system. The 3D force microscope uses magnetic fields to apply forces to ferromagnetic and paramagnetic spheres, and forward light scattering to track the particle. We have designed a tetrahedral electromagnetic pole geometry using finite element analysis to model the fields and forces. With pole spacing of 350 microns, we are able to generate over 100 pN of force with air-cooled coils. A tracking algorithm allows the particle to be tracked within the 100 micron x 100 micron x 15 micron range of the sample stage while the forward light scattering signal allows position measurements with high spatial resolution (<10nm) and bandwidth exceeding 10kHz. The microscope has been interfaced to a haptic (force feedback) interface that allows the positioning of the particle using a hand held pen. Motion of the pen in 3D controls the coil currents, and hence the applied force, and the force is displayed to the user hand through motors that drive the pen. We present results from our initial applications in the viscoelasticity of mucus and cell studies.
Ethics and HRD: A New Approach to Leading Responsible Organizations

The article presents a review of the book “Ethics and HRD: A New Approach to Leading Responsible Organizations,” by Tim Hatcher.
On Educating Schizophrenics About Schizophrenia

Hospitalized schizophrenics attended a class on schizophrenia (1) to learn about their illness; (2) to try to understand why they are sometimes labeled schizophrenic and sometimes not; and (3) to try to determine the validity of their diagnosis. Many attendees appreciated the class while others, by not attending the second of two sessions, raised questions about its appropriateness for them.
HEMOCHROMATOSIS. A REPORT OF THREE CASES WITH RESULTS OF INSULIN THERAPY IN ONE CASE

Hemochromatosis is a rather rare disease characterized by deposition of pigment in the skin and various organs, cirrhosis of the liver, and often progressive sclerosis of the pancreas with severe diabetes mellitus. The first clinical description of the disease was published by Hanot and Chauffard in 1882. The name “hemochromatosis” was given to it by von Recklinghausen, who found that the pigmentation of the various organs in this condition was due to two pigments, hemosiderin and hemofusein, of which the first is iron containing. The comparative rarity of hemochromatosis is shown by the fact that only three cases of it occurred in over 60,000 admissions to the University of California Hospital, and but the same number of cases was found among 106,000 medical admissions to the Johns Hopkins Hospital. Seventy-five cases of hemochromatosis were described in the literature up to 1918, and since that time fifty-one new cases have been reported. The disease attacks males mostly, as only five authenticated typi...