cssi/SciSciGPT-SciSciNet huggingface dataset:
CpcM Posttranslationally Methylates Asparagine-71/72 of Phycobiliprotein Beta Subunits in Synechococcus sp. Strain PCC 7002 and Synechocystis sp. Strain PCC 6803

Cyanobacteria produce phycobilisomes, which are macromolecular light-harvesting complexes mostly assembled from phycobiliproteins. Phycobiliprotein beta subunits contain a highly conserved gamma-N-methylasparagine residue, which results from the posttranslational modification of Asn71/72. Through comparative genomic analyses, we identified a gene, denoted cpcM, that (i) encodes a protein with sequence similarity to other S-adenosylmethionine-dependent methyltransferases, (ii) is found in all sequenced cyanobacterial genomes, and (iii) often occurs near genes encoding phycobiliproteins in cyanobacterial genomes. The cpcM genes of Synechococcus sp. strain PCC 7002 and Synechocystis sp. strain PCC 6803 were insertionally inactivated. Mass spectrometric analyses of phycobiliproteins isolated from the mutants confirmed that the CpcB, ApcB, and ApcF were 14 Da lighter than their wild-type counterparts. Trypsin digestion and mass analyses of phycobiliproteins isolated from the mutants showed that tryptic peptides from phycocyanin that included Asn72 were also 14 Da lighter than the equivalent peptides from wild-type strains. Thus, CpcM is the methyltransferase that modifies the amide nitrogen of Asn71/72 of CpcB, ApcB, and ApcF. When cells were grown at low light intensity, the cpcM mutants were phenotypically similar to the wild-type strains. However, the mutants were sensitive to high-light stress, and the cpcM mutant of Synechocystis sp. strain PCC 6803 was unable to grow at moderately high light intensities. Fluorescence emission measurements showed that the ability to perform state transitions was impaired in the cpcM mutants and suggested that energy transfer from phycobiliproteins to the photosystems was also less efficient. The possible functions of asparagine N methylation of phycobiliproteins are discussed.
Words, Images, Artifacts and Sound: Documents for the History of Technology

‘In the beginning was the Word…and the Word was God’. These words—taken out of their theological context—epitomize a common attitude among historians during most of Western history. By definition, there was no history before the advent of writing. Truly, for history, ‘in the beginning was the Word’ and, for nearly six millenia for the historian, ‘the Word was God’. As a consequence, words have dominated both the content and the form of historical works, including documentary editions. The close historical identity between reality and the mind and between ideas and words has reinforced the focus on words. There remain today philosophers who argue that thinking can only occur with words. It is not surprising, then, that a verbal conception of documents continues to dominate historical documentary editing. A few years ago, a famous American historian and documentary editor sought to convince me that documents were by definition, verbal.
Vascular Disorders of the Liver

Hepatic vascular disorders are a set of conditions that may be acute, or may be insidious and subclinical for many years. They can be organized into 3 categories: obstruction to hepatic vascular inflow, obstruction to blood flow through the liver, and obstruction to hepatic vascular outflow. In the first category are portal vein thrombosis, hepatic artery thrombosis, and presinusoidal causes of vascular obstruction. In the second category are sickle cell disease, disseminated intravascular coagulation, intrasinusoidal malignancy, and infection. In the third category are macroscopic hepatic venous thrombosis, thrombosis of the retrohepatic inferior vena cava, and venoocclusive disease. There are 2 nodular conditions of the liver that are not neoplastic but the result of occlusion of hepatic vasculature with compensatory hyperplasia of well-vascularized parenchyma. Hepatic vascular disorders constitute a heterogeneous group of conditions that must be considered in the differential diagnosis of any patient with hepatic compromise.
Degradation of isofenphos in cornfields with conservation tillage practices

Abstract Isofenphos (Amaze®, Oftanol®, 1‐methylethyl 2‐[[ethoxy‐[(l‐methylethyl)aminol phosphinothloyl]oxy]benzoate) was applied at planting to study the effects of four different tillage treatments (no‐tillage, fall chisel plow, Paraplow®, and fall moldboard plow) on isofenphos degradation rates and routes in cornfields over two growing seasons. Soil samples were taken at intervals extending over 69 days each growing season. Tillage treatment had no significant effect on isofenphos degradation rates and products. However, the repeated application of isofenphos had a very significant effect on lsofenphos degradation. Degradation was much more rapid the second year. A laboratory experiment comparing sterile and nonsterlle soils, with and without isofenphos history, confirmed enhanced mlcrobial degradation resulting from two consecutive years of isofenphos application. In the first year, isofenphos oxon was found at greater amounts relative to the second year. Soil bioassays conducted on soils collected fro...
The myosin filament XIV backbone structure.

The substructure of the thick filaments of chemically skinned chicken pectoralis muscle was investigated by electron microscopy. Images of transverse sections of the myosin filaments were determined to have threefold symmetry by cross-correlation analysis, which gives an unbiased determination of the rotational symmetry of the images. Resolution, using the phase residual test (Frank et al. 1981. Science [Wash. DC]. 214:1353–1355), was found to be between 3.2 and 3.6 nm. Three arrangements of nine subfilaments in the backbone were found in all regions of the filament at ionic strengths of 20 and 200 mM. In the average images of two of these, there were three dense central subfilaments and three pairs of subfilaments on the surface of the thick filament. In the average image of the third arrangement, all of the protein mass of the nine subfilaments was on the surface of the filament with three of them showing less variation in position than the others. A fourth arrangement appearing to be transitional between two of these was seen often at 200 mM ionic strength and only rarely at 20 mM. On average, the myosin subfilaments were parallel to the long axis of the filament. The different arrangements of subfilaments appear to be randomly distributed among the filaments in a transverse section of the A-band. Relative rotational orientations with respect to the hexagonal filament lattice, using the three densest subfilaments as reference showed a major clustering (32%) of filaments within one 10 degrees spread, a lesser clustering (15%) at 90 degrees to the first, and the remainder scattered thinly over the rest of the 120 degrees range. There was no obvious pattern of distribution of the two predominant orientations that could define a superlattice in the filament lattice.
Negative magnetoresistance of pitch-based carbon fibers Temperature and pressure dependence

The negative transverse magnetoresistance of high-modulus pitch-based carbon fibers has been measured over the temperature range 1.3-4.2 K at ambient pressure and at 4.2 K under hydrostatic pressure up to 16 kbar. At low fields (less than 0.5 torr) the magnitude of the magnetoresistance increases markedly as the temperature is lowered from 4.2 K to 1.3 K, in disagreement with Bright's theoretical model, and decreases with pressure at the rate -0.6 percent/kbar.
LDA modeling of the electronic structure of the halogen-bridged transition-metal chain compounds

The electronic-structure for the halogen-bridged transition-metal (MX) linear chain compound Pt 2 X 6 (NH 3 ) 4 (X = Cl, Br, I) under uniaxial stress is studied using the full-potential linear muffin-tin method within the local density approximation. We have found that the ground state of the full structure (with the ammonia ligands) is insulating with a strong lattice distortion in good agreement with experiment. This highlights the importance of the ligand structure to the stability of MX systems and to its ground state nature. The amplitude of the charge density wave in these systems as a function of the metal-metal distance produced a linear shift of the core level energies of the two non-equivalent metal sites. This core level energy shift could be checked experimentally using X-ray absorption spectroscopy. The band structure along the chain is dominated by a strong coupling (pdσ) between Pt(d 3z 2 ―r 2) and X(p z ) orbitals, which causes the system to be of a quasi-one-dimensional character. The relevant band structure as a function of the metal-metal distance is nicely fitted to a two band tight-binding Su-Schrieffer-Heeger Hamiltonian with a single set of parameters. This model revealed that the mechanism of the dimerization is a consequence of a competition between a strong electron-phonon coupling along the chain and a repulsive anharmonic potential.
Tunable-frequency high-field electron paramagnetic resonance

A tunable-frequency methodology based on backward wave oscillator sources in high-frequency and -field EPR (HFEPR) is described. This methodology is illustrated by an application to three non-Kramers transition metal ion complexes and one Kramers ion complex. The complexes are of: Ni(II) (S = 1) as found in dichlorobistriphenylphosphanenickel(II), Mn(III) (S = 2) as found in mesotetrasulfonatoporphyrinatomanganese(III) chloride, Fe(II) (S = 2) as found in ferrous sulfate tetrahydrate, and Co(II) (S = 3/2) as found in azido(tris(3-tert-butylpyrazol-1-yl)hydroborate)cobalt(II). The above Ni(II) and Mn(III) complexes have been studied before by HFEPR using the multifrequency methodology based on Gunn oscillator sources, but not by the present method, while the Fe(II) and Co(II) complexes presented here have not been studied by any form of HFEPR. Highly accurate spin Hamiltonian parameters can be obtained by the experimental methodology described here, in combination with automated fitting procedures. This method is particularly successful in determining g-matrix parameters, which are very difficult to extract for high-spin systems from single frequency (or a very limited set of multi-frequency) HFEPR spectra, but is also able to deliver equally accurate values of the zero-field splitting tensor. The experimental methods involve either conventional magnetic field modulation or an optical modulation of the sub-THz wave beam. The relative merits of these and other experimental methods are discussed.
Helium-3 and deuterium in back-arc basalts: Lau Basin and the Mariana Trough

Samples of fresh basalt glass from the Mariana Trough and the Lau Basin were analyzed for their isotopic composition of water and helium in order to identify the sources of the volatiles in back-arc basin basalts. In the Mariana Trough basalts, the concentration (0.64–2.1 wt.%) and D/H ratio (δD = −46 to −32‰) of the water provide important evidence for a water-rich component from the subducting lithosphere. Extrapolation to infinite water content gives an end-member D/H ratio ofδD = −25‰.3He/4He ratios are, in general, similar to MORB values (8 RA) and indicate that Mariana Trough basalts represent a mixture of a MORB-type mantle and an alkali and water-rich component from the descending slab. In contrast, the Lau Basin produces both hydrous (1.3 wt.% H2O) and relatively anhydrous (0.12–0.35 wt.%) basalts. The D/H ratio (δD = −43‰) in the hydrous Lau Basin basalt resembles those of Mariana Trough lavas. The low water contents (0.12–0.35 wt.%) and MORB-like D/H ratios (δD = −63 to −70‰) in three of five Lau Basin samples show that the water-rich component, observed in all Mariana Trough lavas, is absent in some Lau Basin lavas and not essential for the production of back-arc basalts. The high3He/4He ratio of Rochambeau Bank in the northern Lau Basin (11 RA), confirms an earlier analysis by Lupton and Craig and provides evidence for an enriched mantle source region beneath the Lau Basin which is perhaps related to the high-3He Samoan “hotspot”.
Andragogy in community college communication courses

This article describes basic orientations of adult learners, developmental stages that may influence learning in community college level instruction, and ways the speech communication program is especially suited to meet the needs of the adult learner.
Preparation and thermal analysis of cotton–clay nanocomposites

Nanocomposites were produced from cotton with montmorillonite clay used as the nanofiller material. Three exfoliation and intercalation methods with different solvents and clay pretreatment techniques were tested for the production of these organic–inorganic hybrids. The method that resulted in superior clay–cotton nanocomposites used a clay pretreatment with 4-methylmorpholine-N-oxide as the cotton solvent. The nanocomposites showed significant improvements in the thermal properties in comparison with unbleached cotton and cotton processed under the conditions for nanocomposite preparation. The degradation temperature of the nanocomposites increased by 45°C, and the char yields for some compositions were twice those of unbleached cotton. The crystalline melt of the materials decreased by 15°C. Future research will include the development of textiles based on these cotton–clay materials and testing for flame-retardant properties and product strength. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2125–2131, 2004
Complications of intrathecal drug delivery systems

Cancer and its treatments often result in complex combinations of nociceptive and neuropathic pain. Comprehensive pharmacologic management with opioids and antineuropathic medications can result in adequate pain control in a vast majority of patients. For patients who fail oral pharmacotherapy, intrathecal drug delivery systems can be used to treat pain from a localized source. When considering a patient for trial and possible implementation of an intrathecal drug delivery system, the risks associated with this invasive therapy must be weighed against the benefits and presented to the patient.
Laparoscopic cholecystectomy: Experience of a single surgeon

Gallbladder removal using laparoscopic techniques has rapidly been adopted by surgeons around the world. Questions have been raised concerning laparoscopic cholecystectomy, including the safety of the operation, its implications for management of common bile duct stones, and the means by which surgeons should be trained. In the present series, 424 patients were referred to a single surgeon for cholecystectomy during a 22-month period. A traditional open cholecystectomy was performed in 9 patients (2.1%) because of presumed contraindications to laparoscopic cholecystectomy. Laparoscopic cholecystectomy was attempted in the remaining 415 patients (97.9%). On the basis of preoperative investigations, 19 patients (4.6%) underwent endoscopic retrograde cholangiopancreatography. Endoscopic sphincterotomy and stone extraction were performed in the 13 patients (3.1%) demonstrating choledocholithiasis. Laparoscopic cholecystectomy was converted to an open operation in 8 patients (1.9%) owing to dense adhesions, obscure anatomy, or cholangiographic abnormalities. Laparoscopic cholecystectomy was successfully performed in 407 patients (96%) in 95 +/- 2 minutes (mean +/- SEM). Surgical trainees were involved in all operations and performed 68% of the procedures under supervision. Cystic duct cholangiograms were obtained selectively in 129 patients (30.4%). Intraoperative complications occurred in 3 patients, including 1 patient with a minor injury to the common bile duct (0.2%). There was no perioperative mortality, and major complications occurred in 6 patients (1.4%). Minor complications were seen in 12 others (2.8%), and one patient required reoperation for a trocar injury to the jejunum. Prolonged follow-up has revealed one case of asymptomatic retained common bile duct stones (0.2%). Laparoscopic cholecystectomy can therefore be performed in more than 95% of patients with no mortality and minimal morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)
Spectral analysis of randomly distributed scatterers for ultrasonic grain size estimation

Abstract Since the average grain size is an important parameter in material characterization, the non-destructive evaluation of the microstructure in polycrystalline materials using ultrasonic backscattered echoes has significant practical implications. However, the complexity of the ultrasonic backscattered signal, which consists of interrering multiple echoes with random positions and amplitudes, makes accurate grain size evaluation difficult with conventional signal processing techniques. This Paper introduces an alternative approach which examines the spectrum of an ensemble of randomly distributed scatterers with known distribution to establish a relationship between the spectral and temporal statistical properties of the scatterers. Theoretical derivations based on a one-dimensional point scattered model show that the average grain size can be extracted from the power spectrum of the backscattered echoes. Using a non-linear least-squares technique, the theoretical grain power spectrum is curve-fitted to the sample grain power spectrum to estimate the mean and standard deviation of the grain size. Computer simulations based on this technique show that the average grain size can be extracted from the power spectrum of the backscattered echoes, indicating the potential feasibility of this technique for material characterization.
Nitrogen solubility and N-induced defect complexes in epitaxial GaAs : N

Previous calculations suggested low-equilibrium N solubility in bulk GaAs. In epitaxial growth, however, N solubility can be significantly enhanced to as much as a few %. First-principles total-energy calculations show that this large difference is due to the lack of low-energy nucleation sites of GaN during epitaxy. As a result, the atomic chemical potential of N can be significantly larger. This gives rise to new defect physics distinctly different from those in GaAs.
Muslim Women's Rights in the Global Village: Challenges and Opportunities

In this age of information technology that shrank our world into a global village, it is fair to ask how this recent development has impacted Muslim women's rights across the world. Having just traveled through nine Muslim countries, ranging from Pakistan and Bangladesh to the Gulf States, Egypt, Syria, and Lebanon, I would answer that it is leading, slowly but surely, to reassessment and change. Attempts to accelerate the pace of this change, however, without full understanding of its complex topology, and the deep-rooted commitment by most Muslim women to spiritual and cultural authenticity, could halt or even reverse this process at great cost to women particularly and Muslim societies as a whole. Hence the challenges and opportunities.
Multiple Three-Decision Rules for Parametric Signs

Abstract Rules are considered for deciding, subject to a global error bound, whether each of several parameters is positive. In general, the decision “inconclusive data,” in addition to “positive” and “negative,” must be allowed in order to achieve the error bound. Rules based on multiple, one-sided t tests are defined, with critical points evaluated for important special cases. Conditions under which these rules are optimal are established. Examples in factorial experimentation are considered, and some extensions are discussed.
Ship wake-detection procedure using conjugate gradient trained artificial neural networks

A method has been developed to reduce large two-dimensional images to significantly smaller feature lists. These feature lists overcome the problem of storing and manipulating large amounts of data. A new artificial neural network using conjugate gradient training methods, operating on sets of feature lists, was successfully trained to determine the presence or absence of wakes in synthetic aperture radar images. A comparison has been made between the different conjugate gradient and steepest-descent training methods and has demonstrated the superiority of the former over the latter. >
“What Bothers You the Most?” Initial Responses From Patients Receiving Palliative Care Consultation

The purpose of this investigation is to describe how hospitalized palliative care patients respond to the question "What bothers you the most?" at the time of initial consultation. A retrospective descriptive content analysis of first person responses routinely recorded during initial interview (n = 286) was carried out. Responses were grouped in 7 major categories: physical distress (44%); emotional, spiritual, existential, or nonspecific distress (16%); relationships (15%); concerns about the dying process and death (15%); loss of function and normalcy (12%); distress about location (11%); and distress with medical providers or treatment (9%). Fifteen percent of responses were unable to be reliably categorized. Although many of our patients were not able to answer open-ended questions because of illness, those who did shared a wide range of concerns that provided a starting point for clinical prioritization. Further research into the use of such simple questions at time of initial consultation is warranted.
Audio streaming over Bluetooth: an adaptive ARQ timeout approach

Streaming audio has become a popular form of media on the Internet. As wireless personal area network architectures (e.g. Bluetooth) are now targeted to support multimedia traffic, streaming audio over these technologies give rise to interesting applications. But, the variable nature of the wireless medium will not lend itself easily to supporting audio streaming. We focus on Bluetooth and propose, an enhancement to the Bluetooth link layer ARQ mechanism to compensate for channel degradation and to better support audio streaming. Specifically, our scheme adoptively sets the ARQ timeout value based on current channel measurements. We show through testbed experiments that the adaptive ARQ improves the streaming quality significantly compared to the "vanilla" link layer of Bluetooth, especially in noisy environments. Our proposed approach is simple to implement and can actually be extended to the link layer of any wireless technology.
Do Facilities with Distant Headquarters Pollute More? How Civic Engagement Conditions the Environmental Performance of Absentee Managed Plants

Scholars agree that due to advances in transportation and communication technologies, firms can extend their reach and more easily externalize their pollution by setting up plants in far-flung, less regulated areas. They also concur that absentee managed plants or facilities with remote headquarters are rapidly becoming the modal type of industrial organization. However, they have yet to examine the environmental performance of these plants and how their propensity to pollute is conditioned by the types of communities that harbor them. This reflects a more general failure on the part of social scientists to study the impact that different organizational forms have on the physical environment. Using the EPA's newly published 2000 Toxics Release Inventory, we test the direct and interactive effects of absentee management on the environmental performance of chemical plants in the U.S. Findings reveal that absentee managed plants emit more toxins, on average, than other plants. However, when we take into account the amount of chemicals that plants have on-site and other factors that influence facilities' emissions, we discover that the environmental performance of absentee managed plants is no worse than that of other plants. Whether plants with distant headquarters emit more toxins largely depends on the presence of local institutions that facilitate civic engagement. When embedded in communities with more associations, churches, and "third places," absentee managed plants emit significantly fewer toxins. [End Page 189]
The CAPP terminal device, size 2: a new alternative for adolescents and adults.

CAPP Terminal Device, Size #2 for teenaged and adult amputees offers an alternative to hooks and hands available today. CAPP TD 2 is intended to be pleasing in appearance; it blends with the forearm in shape, colour and material to give a continuous flowing natural look. It was designed to provide secure grip through the combined action of a closing spring, a full frictional, resilient cover and an automatic lock. The lock operates as part of the voluntary opening control system and requires no conscious action by the amputee. CAPP TD 2 is a general purpose terminal device which especially serves unilateral amputees by performing functions usually carried out by the non-dominant hand. CAPP TD 2 comes with a built-in wrist connector which is available in two models; both offer quick disconnect. One wrist unit has adjustable friction and the other attaches to an existing friction wrist unit so CAPP TD 2 can be applied to an existing prosthesis. Ten patients have completed the evaluation programme with promi...
Friendship, Real–Ideal Discrepancies, and Well-Being: Gender Differences in College Students

ABSTRACT Do men and women have different ideals for their friendships? What do men and women experience when their actual friendship experiences fall short of their ideals? The authors of the current study investigated gender differences in real–ideal same-sex best friendships and friendship discrepancy scores. Correlates of friendship discrepancies were also examined. For this purpose, a sample of 382 college students completed the McGill Friendship Questionnaire (M. J. Mendelson & F. E. Aboud, 1999), the Friendship Conflict Scale (M. Demir & L. A. Weitekamp, 2007), the Need Satisfaction Scale (J. G. La Guardia, R. M. Ryan, C. E. Couchman, & E. L. Deci, 2000), and the PANAS (D. Watson, L. A. Clark, & A. Tellegen, 1988). Results showed that (a) the real and ideal best friendships of women were higher in quality and lower in conflict when compared to those of men; and (b) men's discrepancy scores for friendship quality were significantly higher when compared to women, whereas no differences were obtained o...
Female Gender Attenuates Cytokine and Chemokine Expression and Leukocyte Recruitment in Experimental Rodent Abdominal Aortic Aneurysms

Female gender appears to be protective in the development of abdominal aortic aneurysms (AAAs). This study sought to identify gender differences in cytokine and chemokine expression in an experimental rodent AAA model. Male and female rodent aortas were perfused with either saline (control) or elastase to induce AAA formation. Aortic diameter was determined and aortic tissue was harvested on postperfusion days 4 and 7. Cytokine and chemokine gene expression was examined using focused gene arrays. Immunohistochemistry was used to quantify aortic leukocyte infiltration. Data were analyzed by Student's t-tests and ANOVA. Elastase-perfused female rodents developed significantly smaller aneurysms compared to males by day 7 (93 +/- 10% vs. 201 +/- 25%, P = 0.003). Elastase-perfused female aortas exhibited a fivefold decrease in expression of the BMP family and ligands of the TNF superfamily compared to males. In addition, the expression of members of the TGF beta and VEGF families were three to fourfold lower in female elastase-perfused aortas compared to males. Multiple members of the interleukin, CC chemokine receptor, and CC ligand families were detectable in only the male elastase-perfused aortas. Female elastase-perfused aortas demonstrated a corollary twofold lower neutrophil count (females: 17.5 +/- 1.1 PMN/HPF; males: 41 +/- 5.2 neutrophils/HPF, P = 0.01) and a 1.5-fold lower macrophage count (females: 12 +/- 1.1 macrophages/HPF; males: 17.5 +/- 1.1 macrophages/HPF, P = 0.003) compared to male elastase-perfused aortas. This study documents decreased expression of multiple cytokines and chemokines and diminished leukocyte trafficking in female rat aortas compared to male aortas following elastase perfusion. These genes may contribute to the gender disparity seen in AAA formation.
Simulation of microfocused image size from a one-bounce glass capillary

Abstract A new method of numerical calculation, based on geometrical optics for X-rays rather than ray-tracing, is developed to simulate the focal spot size and intensity gain from an elliptically-tapered one-bounce glass mono-capillary. Numerical results for a capillary designed for protein crystallography are in good agreement with experimental measurements and confirm a capillary slope errors limitation on the image quality.
Expression of Nrf2 in Neurodegenerative Diseases

In response to oxidative stress, the nuclear factor E2-related factor 2 (Nrf2) transcription factor translocates from the cytoplasm into the nucleus and transactivates expression of genes with antioxidant activity. Despite this cellular mechanism, oxidative damage is abundant in Alzheimer and Parkinson disease (AD and PD). To investigate mechanisms by which Nrf2 activity may be aberrant or insufficient in neurodegenerative conditions, we assessed Nrf2 localization in affected brain regions of AD, Lewy body variant of AD (LBVAD), and PD. By immunohistochemistry, Nrf2 is expressed in both the nucleus and the cytoplasm of neurons in normal hippocampi with predominant expression in the nucleus. In AD and LBVAD, Nrf2 was predominantly cytoplasmic in hippocampal neurons and was not a major component of beta amyloid plaques or neurofibrillary tangles. By immunoblotting, we observed a significant decrease in nuclear Nrf2 levels in AD cases. In contrast, Nrf2 was strongly nuclear in PD nigral neurons but cytoplasmic in substantia nigra of normal, AD, and LBVAD cases. These findings suggest that Nrf2-mediated transcription is not induced in neurons in AD despite the presence of oxidative stress. In PD, nuclear localization of Nrf2 is strongly induced, but this response may be insufficient to protect neurons from degeneration.
The biochemistry of RNA metabolism studied in situ

In vitro assays have contributed important insights into the mechanisms of RNA metabolism in cells. A growing collection of microscopy techniques is allowing the measurement of macromolecular binding and complex formation in the context of a real cell. We will first discuss two of the more established techniques. Fluorescence resonance energy transfer (FRET) identifies binding partners, pairs of molecules residing in the same macromolecular complexes. The complimentary technique of fluorescence recovery after photobleaching (FRAP) measures the rates of binding and unbinding of those molecules in their complexes. A newer technique--in vitro FRAP--assesses the regulation of binding and complex formation by co-factors in the nucleus.
Using metabotropic glutamate receptors to modulate cocaine's synaptic and behavioral effects: mGluR1 finds a niche

Group I metabotropic glutamate receptors (mGluR) are important modulators of excitatory synaptic transmission and therefore potential targets for drug development. In several brain regions (ventral tegmental area (VTA), cerebellum, and amygdala), stimulation of mGluR1 selectively inhibits synaptic transmission mediated by calcium-permeable AMPA receptors (CP-AMPARs) and thus produces synaptic depression. The same relationship has now been demonstrated in the nucleus accumbens (NAc), a region that is critical for cocaine craving. CP-AMPAR levels in NAc synapses are normally low, but they increase after prolonged withdrawal from extended-access cocaine self-administration (SA). These CP-AMPARs mediate the intensified (‘incubated’) cue-induced cocaine craving observed under these conditions. Therefore, activation of mGluR1 with positive allosteric modulators (PAM) may reduce cue-induced relapse in abstinent cocaine addicts.
ZnO Nanotip-based QCM Biosensors

The medical diagnostics laboratories are showing an urgent need for accurate, fast and inexpensive biosensors. A zinc oxide (ZnO) nanotip-based quartz crystal microbalance (QCM) sensor is developed as a solution for accurate and inexpensive biosensors. The QCM sensor composed of single crystalline ZnO nanotips grown on top of a gold electrode using metal-organic chemical vapor deposition (MOCVD). Scanning electron microscopy (SEM) shows that the ZnO nanotips are uniformly aligned with their c-axis normal to the gold surface, giving a large surface area for sample up-taking. The ZnO nanotip coated QCM sensor shows a 10-time larger frequency shift than that of regular QCM sensors, when measuring the same DNA oligonucleotide (5'-AGAAAATCTTAGTGTC-3') solution. In addition, the hydrophilic behaviors of the nanotip array significantly reduce the required liquid volume for effective detection. 0.5 mul solution fully covers the QCM sensor area (0.2047 cm2), while a minimum of 16 mul liquid is required to cover a flat surface of the conventional QCM. ZnO nanotips show superhydrophilicity with a contact angle of ~0deg under ultraviolet (UV) illumination. The superhydrophilic sensor surface significantly boosts the solution taking up ability; therefore, enhances the sensitivity of the QCM sensor. The effects of ZnO nanostructure on the bulk acoustic wave (BAW) are also discussed
Competition Breeds Desire

Desire spurs competition; here we explore whether the converse is also true. In one study, female quartets (N = 58) completed anagrams, with the winner to receive compact speakers; controls anagrammed without competition. In the other study, female quartets (N = 74) described their ideal first date to a male judge, who chose the best description; controls read to him others' date descriptions without competition. In both studies, creating competition increased desire and altered how much participants wanted, but not how much they liked, the competed-for thing. Competition may activate a general “wanting system,” producing overvaluing in settings from stock markets to partner selection.
Improved CFD modeling of a small data center test cell

An improved CFD model is presented to predict the thermal field in a small data center test cell. CFD analysis reported in an earlier paper [19] tended to exaggerate hot and cold spots in a small data center test cell as a result of the inability of the CFD model to predict the correct level of mixing of the cold air emanating from the perforated floor tiles and the warmer room air. The same can be said about the mixing of the hot air stream exiting the rack and the surrounding room air. The overall RMS error in the earlier study was 4°C between numerical results and test data. Another indication of low mixing in the CFD results is illustrated in the comparison of the temperature profile along a vertical line in front of the rack between CFD results and test data. While the temperature of the cold flow from the under floor plenum entering the data center was measured to be 12.8°C, temperature measurement at the same location via a temperature mapping tool showed that it is 15°C at 6" above the floor and rising quickly to 17°C at a height of 4 ft. The present investigations yield several improvements to the CFD model, including modeling of the perforated tile flow and rack exhaust flow to conserve both mass and momentum, inclusion of the effects of buoyancy, and an improved thermal boundary condition for the floor. With these improvements, the overall RMS error was reduced to 2°C between numerical results and the same test data reported in [19].
Early and chronic treatment with dantrolene blocked later learning and memory deficits in older Alzheimer's triple transgenic mice

Background: The major neuropathological hallmarks in the brains of AD patients are senile plaques formed by beta amyloid (As) aggregates and neurofibrillary tangles, containing hyperphosphorylated tau, both causing progressive neuronal dysfunction. These pathological alterations are likely causally involved in eventual neuronal death, particularly in brain regions related to memory and cognition. The first attempt to develop an active vaccine to As, AN1793, failed in clinical trials due to a Th1 type T cell immune response, attributed to the adjuvant used, QS21 and polysorbate 80, provoking a meningoencephalitis-like effect and death in 6% of the patients. To overcome this failure, we designed a novel As1-42 active vaccine incorporated and delivered in a liposomal adjuvant that evoked aTh2 T cell reaction. Methods: As was incorporated and delivered in a liposomal matrix composed of phosphatidylcholine: phosphatidylglycerol: cholesterol:sphingosine-1-phosphate (EB101) and administered intraperitoneally for seven months to double transgenic mice (B6C3-Tg (APPswe,PSEN1dE9)), before or after the AD pathology was developed (In 7-week and 37-week old mice respectively). As plaques and neurofibrillary tangles were quantified by ELISAs and brain histology using specific antibodies. Basal immunological interaction between the T-cells in the affected hippocampalarea and other immune activation markers, including glial fibrillary acidicprotein (GFAP) (astroglia) and CD-45 (B-cells) were also studied using immunoreactive-specific staining. T-cell reaction type was assessed by cytokine type production. Results: Both preventive and therapeutic vaccination with EB101 resulted in a marked inhibition of As deposits (60 to 80%), a reduction of neurofibrillary tangles (70 to 90%) and almost completely suppression of reactive gliosis as measured by GFAP immunoreactivity and cytokine profile, consistent with a marked decrease in amyloidosis-induced inflammation. No external neurological deficits were observed as a result of EB101 immunization (limb paralysis or brain atrophy). Psychomotor and cognitive tests performed in a rota-rod in these animals also showed a dramatic improvement in learning and psychomotor activity in the EB101-treated group. Conclusions: The present findings unequivocally indicate that immunization with EB101 not only prevents and reverses AD neuropathology and underlined inflammation, but also improves cognitive symptoms, thus warranting further studies.
Restitution of Tumor Suppressor MicroRNAs Using a Systemic Nanovector Inhibits Pancreatic Cancer Growth in Mice

Misexpression of microRNAs (miRNAs) is widespread in human cancers, including in pancreatic cancer. Aberrations of miRNA include overexpression of oncogenic miRs ("Onco-miRs"), or downregulation of so-called tumor suppressor "TSG-miRs". Restitution of TSG-miRs in cancer cells through systemic delivery is a promising avenue for pancreatic cancer therapy. We have synthesized a lipid-based nanoparticle for systemic delivery of miRNA expression vectors to cancer cells ("nanovector"). The plasmid DNA-complexed nanovector is ~100nM in diameter, and demonstrates no apparent histopathological or biochemical evidence of toxicity upon intravenous injection. Two miRNA candidates known to be downregulated in the majority of pancreatic cancers were selected for nanovector delivery: miR-34a, which is a component of the p53 transcriptional network and regulates "cancer stem cell" (CSC) survival, and the miR-143/145 cluster, which together repress the expression of KRAS2, and its downstream effector Ras-responsive element binding protein-1 (RREB1). Systemic intravenous delivery with either miR-34a or miR-143/145 nanovectors inhibited the growth of MiaPaCa-2 subcutaneous xenografts (P<0.01 for miR-34a, P<0.05 for miR-143/145); the effects were even more pronounced in the orthotopic (intra-pancreatic) setting (P<0.0005 for either nanovector), when compared to vehicle or "mock" nanovector delivering an empty plasmid. Tumor growth inhibition was accompanied by increased apoptosis and decreased proliferation. MiRNA restitution was confirmed in treated xenografts by significant upregulation of the corresponding miRNA, and significant decreases in specific miRNA targets (SIRT1, CD44 and aldehyde dehydrogenase for miR34a, and KRAS2 and RREB1 for miR-143/145). The nanovector is a platform with potential broad applicability in systemic miRNA delivery to cancer cells.
Costs of a public health model to increase receipt of hepatitis-related services for persons with mental illness.

ObjectiveThis study examined the costs and impact on receipt of hepatitis and HIV testing and hepatitis immunization services of a public health intervention model that was designed for use by persons with serious mental illness and co-occurring substance use disorders.MethodsBetween 2006 and 2008, a random sample of 202 nonelderly, predominantly African-American males with a psychotic or major depressive disorder and a co-occurring substance use disorder was recruited at four community mental health outpatient programs in a large metropolitan area. Participants were randomly assigned at each site to enhanced treatment as usual (N=97), including education about blood-borne diseases and referrals for testing and vaccinations, or to an experimental intervention (N=105) that provided on-site infectious disease education, screening of risk level, pretest counseling, testing for HIV and hepatitis B and C, vaccination for hepatitis A and B, and personalized risk-reduction counseling. The authors compared the tw...
The next frontier: interactive and closed loop performance steering

Software for a growing number of problem domains has complex, time varying behavior and unpredictable resource demands (e.g., WWW servers and parallel input/output systems). While current performance analysis tools provide insights into application dynamics and the causes of poor performance, with a posteriori analysis one cannot adapt to temporally varying application resource demands and system responses. We believe that the solution to this performance optimization conundrum is integration of dynamic performance instrumentation and on-the-fly performance data reduction with real-time adaptive control mechanisms that select and configure resource management algorithms automatically, based on observed application behavior, or interactively, through high-modality virtual environments. We motivate this belief by first describing our experiences with performance analysis tools, input/output characterization, and WWW server analysis, and then sketching the design of interactive and closed loop adaptive control systems.
Chronic nicotine‐induced switch in Src‐family kinase signaling for long‐term potentiation induction in hippocampal CA1 pyramidal cells

Here, we show that chronic nicotine exposure induces changes in Src signaling for the modulation of N-methyl-D-aspartate receptor (NMDAR) function and LTP induction in CA1 pyramidal cells. Activation of muscarinic receptors normally potentiates NMDAR responses in pyramidal cells via a Gq/protein kinase C (PKC)/proline-rich tyrosine kinase 2/Src signaling cascade. However, muscarinic, PKC and Src stimulation had no effect on NMDAR responses after chronic nicotine treatment. The lack of effect was apparently due to enhanced tyrosine phosphorylation, and therefore further stimulation of the signaling cascade caused no effect on NMDAR responses. Interestingly, another Src-family kinase potentiated NMDAR responses after, but not before, chronic nicotine treatment. In control pyramidal cells, Src inhibitor peptides prevented tetanus-induced long-term potentiation (LTP). Conversely, in chronic nicotine-exposed cells, the inhibitor was ineffective in blocking tetanus-induced LTP. Furthermore, in control pyramidal cells, applying exogenous Src and administration of an endogenous Src-family kinase activator increased alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR)-mediated responses. This increase was blocked by Src inhibitor peptides and occluded tetanus-induced LTP, as reported previously. In contrast, in chronic nicotine-treated pyramidal cells, applying exogenous Src had no effect on AMPAR-mediated responses and a tetanus-induced LTP. Interestingly, however, administration of an endogenous Src-family kinase activator enhanced AMPAR-mediated responses, which occluded tetanus-induced LTP. This enhancement was not prevented by co-application of Src inhibitor peptides. Thus, it appears that chronic nicotine exposure recruits another member of the Src-family for the regulation of NMDAR function and LTP induction. The nicotine-induced distinct signaling cascades may be involved in long-lasting memories of nicotine misuse.
The effect of offering different numbers of colorectal cancer screening test options in a decision aid: a pilot randomized trial.

Decision aids can improve decision making processes, but the amount and type of information that they should attempt to communicate is controversial. We sought to compare, in a pilot randomized trial, two colorectal cancer (CRC) screening decision aids that differed in the number of screening options presented. Adults ages 48–75 not currently up to date with screening were recruited from the community and randomized to view one of two versions of our previously tested CRC screening decision aid. The first version included five screening options: fecal occult blood test (FOBT), sigmoidoscopy, a combination of FOBT and sigmoidoscopy, colonoscopy, and barium enema. The second discussed only the two most frequently selected screening options, FOBT and colonoscopy. Main outcomes were differences in screening interest and test preferences between groups after decision aid viewing. Patient test preference was elicited first without any associated out-of-pocket costs (OPC), and then with the following costs: FOBT-$10, sigmoidoscopy-$50, barium enema-$50, and colonoscopy-$200. 62 adults participated: 25 viewed the 5-option decision aid, and 37 viewed the 2-option version. Mean age was 54 (range 48–72), 58% were women, 71% were White, 24% African-American; 58% had completed at least a 4-year college degree. Comparing participants that viewed the 5-option version with participants who viewed the 2-option version, there were no differences in screening interest after viewing (1.8 vs. 1.9, t-test p = 0.76). Those viewing the 2-option version were somewhat more likely to choose colonoscopy than those viewing the 5-option version when no out of pocket costs were assumed (68% vs. 46%, p = 0.11), but not when such costs were imposed (41% vs. 42%, p = 1.00). The number of screening options available does not appear to have a large effect on interest in colorectal cancer screening. The effect of offering differing numbers of options may affect test choice when out-of-pocket costs are not considered.
The immunoglobulin kappa light chain repertoire expressed in the synovium of a patient with rheumatoid arthritis.

OBJECTIVE To analyze the nature of the B cell response in the synovial tissue of a patient with rheumatoid arthritis (RA). Specifically, we sought to determine if the pattern of immunoglobulin expression was consistent with polyclonal stimulation of B cells or an antigen-driven response. METHODS We generated an unrestricted complementary DNA (cDNA) library from the diseased synovium of a rheumatoid factor (RF)-positive patient with an 18-year history of RA. A random sample of kappa light chain recombinants was identified, and sequence analysis was performed. The variable domains were compared with an extensive database of germline and cDNA kappa sequences. RESULTS We found a light chain repertoire enriched for kappa transcripts containing 2 V kappa gene segments (Humkv325 and Humkv328) that are frequently associated with paraproteins expressing RF activity. Kappa variable domains from synovium contained numerous somatic mutations which resulted in frequent replacement of amino acids that encode the classic antigen-binding site. Unexpectedly, many of these kappa transcripts contained non-germline-encoded nucleotides (N regions) at the site of V kappa-J kappa joining. The combination of N-region addition and variation in the sites of V kappa-J kappa splicing generated unusually long complementarity-determining region 3 regions and charged amino acids near the V kappa-J kappa splice site. CONCLUSION The pattern of somatic mutations found in this patient sample supports the hypothesis that these synovium-derived plasma cells are the product of immunoglobulin receptor-dependent (i.e., antigen-driven) selection. The extent of N-region addition raised the additional possibility that these antibodies derive from an unusual set of B lymphocytes that have escaped normal regulation.