cssi/SciSciGPT-SciSciNet huggingface dataset:
Structure of transfer RNA by carbon NMR: resolution of single carbon resonances from 13C-enriched, purified species

Methyl carbon-13 NMR spectra of purified tRNA species are presented for the first time. In addition, these spectra of tRNA species specific for phenylalanine, tyrosine, and cysteine exhibited the first resolution of single methyl carbon resonances. Carbon-13 enriched methyl groups of ribothymidine (T) and 7-methylguanosine (m7G) and the methylthio group of 2-methylthio-N6-(delta2-isopentenyl) adenosine (ms2i6A) were resolved. The T methyl signal of tRNAPhe shifted from 12.3 ppm at 45 degrees in the absence of added Mg2+ to 11.1 ppm at 30 degrees in the presence of 10mM MgCl2. The same change in conditions led to a 0.4 ppm shift of the m7G methyl signal in the opposite direction. The relative ease in obtainment of single carbon resonances of purified tRNA species, and display of the sensitivity of their chemical shifts to changes in local structure, are requisite criteria for 13C-NMR to be a useful technique in probing tRNA conformation and its changes during interaction with proteins and other nucleic acids.
Fluxes of vμ and ve in the atmosphere: Is there an anomaly?

Abstract There is a persistent discrepancy between the calculated and observed flavor ratio of cosmic ray neutrinos in the atmosphere, particularly in the energy region below 1 GeV. In this talk I review the status of calculations of atmospheric neutrinos and discuss possible interpretations in terms of neutrino oscillations. Limits from neutrino-induced upward muons are also considered.
An Approach for Developing Flexible MRP Systems

Like most software systems, manufacturing resource planning systems suffer from high maintenance expense. This article examines how object-oriented techniques can be used to develop systems that require less maintenance. Emphasis is placed on reuse to lower postdevelopment costs.
Chromosomal radiosensitivity of Down syndrome lymphocytes at different stages of the cell cycle.

Down syndrome (DS) is one of the most common types of congenital anomalies. In addition to a wide spectrum of developmental abnormalities, DS patients are also highly sensitive to the induction of chromosomal aberrations when their G0 lymphocytes are exposed to ionizing radiation. We conducted the present study to evaluate the effect of X-rays on proliferating lymphocytes from DS and normal individuals. We found that DS lymphocytes were significantly more sensitive to X-ray induction of chromosome aberrations than normal cells, when they were irradiated at the G0, G1 and S phases of the cell cycle. The S phase was the most radiosensitive phase and would lead to extensive cell killing, whereas the G1 phase seemed to be more prone to the induction of chromosome rearrangements that would potentially lead to serious long-term consequences.
Design and Implementation of an Integrated Network and Data Management System for Heterogeneous WSNs

Wireless Sensor Networks (WSNs) are being used in a variety of applications including environmental monitoring, event detection, object tracking, and healthcare applications. Network management of WSNs is one of the key practical challenges that arise from the increasing number of applications and technologies deployed. This work presents the demonstration proposal for a web-based integrated network and data management system that is aimed at: (1) systematically supporting heterogeneous WSNs with a unified management system; (2) presenting a clear separation between WSN management and application functions; and (3) offering management functionalities with a clear user interface.
WINDOW AND OVERLAP PROCESSING EFFECTS ON POWER ESTIMATES FROM SPECTRA

Abstract Fast Fourier transform (FFT) spectral processing is based on the assumption of stationary ergodic data. In engineering practice, the assumption is often violated and non-stationary data processed. Data windows are commonly used to reduce leakage by decreasing the signal amplitudes near the boundaries of the discrete samples. With certain combinations of non-stationary signals and windows, the temporal weighting may attenuate important signal characteristics to adversely affect any subsequent processing. In other words, the window artificially reduces a significant section of the time signal. Consequently, spectra and overall power estimated from the affected samples are unreliable. FFT processing can be particularly problematic when the signal consists of randomly occurring transients superimposed on a more continuous signal. Overlap processing is commonly used in this situation to improve the estimates. However, the results again depend on the temporal character of the signal in relation to the window weighting. A worst-case scenario, a short-duration half sine pulse, is used to illustrate the relationship between overlap percentage and resulting power estimates. The power estimates are shown to depend on the temporal behaviour of the square of overlapped window segments. An analysis shows that power estimates may be obtained to within 0.27 dB for the following windows and overlap combinations: rectangular (0% overlap), Hanning (62.5% overlap), Hamming (60.35% overlap) and flat-top (82.25% overlap).
Trapping and diffusion mechanism in aluminum alloys

We have studied Al(Cu), Al(Mg) and Al(Ag) alloys to determine the μ+ trapping sites, and how impurity distortions affect these sites. Cu (Monovalent) contracts the Al lattice, Mg (divalent) expands it, and Ag (monovalent) has almost no effect. Fitting to a two-state model we obtained a temperature exponent β of 0.93 (26 for zero field and 1.16(14) for a longitudinal, field where β=1 implies a one-phonon induced diffusion process. The measured secon moment in Al(Mg) indicates a changing trapping site, which was confirmed by zero and longitudinal field studies. Comparing the Al(Mg) results with earlier Al(Cu) data, two types of sites can be identified: those which are distant from the defect and depend on the magnitude but not the sign of the deformation, and those close to Mg. Ag produces no lattice distortion, and its weaker depolarization suggests a different trapping mechanism.
Characterization of an enzymatic determination of arsenic(V) based on response surface methodology

Abstract Response surface methodology was used to characterize a new enzymatic method for the determination of arsenic in aqueous solutions. A Box—Behnken three-level fractional factorial experimental design was employed to characterize the reaction-rate response surface as a function of five experimental factors. Interpretation of the results of regression analysis provides an operational description of the analytical method as well as information that can be correlated with the mechanism of the chemical reaction.
Properties of ultrathin gate oxides grown in N2O-based oxidation ambients by rapid thermal processing

Ultra-thin gate oxides grown by rapid thermal processing in N 2 O-based oxidation ambients were evaluated. Gate oxide integrity was improved by incorporating more nitrogen in the thin gate oxides and by diluting oxidation ambients in inert gases.
ISOLATION AND STRUCTURAL IDENTIFICATION OF NINE AVILAMYCINS

Avilamycin is an antibiotic complex produced by cultures of the organism Streptomyces viridochromogenes, strain NRRL 2860. These compounds belong to the orthosomycin family of antibiotics. Structural composition of the major avilamycins and several minor avilamycins are known. Nine additional minor avilamycins, designated F through N, have been isolated via semi-preparative silica gel or reverse-phase high performance liquid chromatography with final purification using a reverse-phase column loading solvent switching technique. 1H NMR and mass spectroscopy, negative ion fast atom bombardment (neg FAB) and electron impact, were used to structurally identify the avilamycins. All of the compounds were microbiologicallyactive and similar in structure to other known avilamycins.
Hydrogen Density Measurements Using an Open-Ended Microwave Cavity

The density measurement of liquid hydrogen and two-phase mixtures of liquid and gaseous hydrogen is considered. This paper describes a complete prototype system that uses an open-ended microwave cavity for making dynamic density measurements of flowing hydrogen in a transfer line. The theory of operation along with test results for both the single- and two-phase cases are presented and discussed.
Pomest’e prozhitki: Muscovite Patriarchy on the Ground

Study of maintenance allotments indicates that, so long as the so-called patriarchal bargain endured, the Muscovite state accepted the responsibility of providing for servitors’ dependents, just as patriarchal discourse demanded that husbands provide for spouses.
Right ventricular function: Methodologic and clinical considerations in noninvasive scintigraphic assessment

Right ventricular function plays an important role in many cardiac disorders. Changes in left ventricular function, right ventricular afterload and preload, cardiac medications and ischemia may affect right ventricular function. Radionuclide ventriculography permits quantitative assessment of regional and global function of the right ventricle. This assessment can be made at rest, during exercise or after pharmacologic interven tions. The overlap between right ventricle and right atrium is a major limitation for gated scintigraphic techniques. The use of imaging with newer short-lived radionuclides may permit more accurate and reproducible assessment of right ventricular function by means of the first pass method. Further work in areas related to improvement of techniques and the impact of right ventricular function on prognosis is needed.
Effect of Location of an Odd Response on Learning a Six-Unit Maze

Learning by 60 hooded rats of 12 patterns in a six-unit multiple T-maze was measured. Each pattern contained one response in the direction opposite to the other five responses, differing only in the location of the odd response. The most and least difficult patterns (errors to criterion) had the odd response in the middle and the first two units of the maze, respectively. The distribution of errors over choice-points varied with maze patterns, which was reflected in a significant interaction of patterns and choice-points. Within a maze pattern the most difficult choice-point was the odd response; perseverative errors were fewer than anticipatory errors, and the latter occurred mostly in the unit preceding the odd response. The applicability of bi-directional or goal gradients to account for the results is discussed.
Smartphone-compatible robust classification algorithm for the Tongue Drive System

In this paper we present several improvements in the Tongue Drive System magnetic sensor signal processing algorithm and its new 8-command classification performance by applying robust pattern recognition techniques that are resistant to natural tongue movements and earth's magnetic field variations. Two additional commands have been added to the system for better compatibility with smartphone interfaces. For this algorithm support vector machine with radial basis function kernels has been proposed instead of the previous algorithm that was based on linear distance discrimination. The proposed algorithm has also been compared with two commonly used nonlinear classifiers, the Neural Network and AdaBoost. Data was collected from six able-bodied subjects while they sat, walked and read a passage. The average false positive ratio while walking and talking was 2.73% error, and the overall system accuracy under normal conditions was 92.64% correctness, 2.87% misclassification error, and 4.49% rejection error.
A mechanism for neuronal gain control by descending pathways

Many implementations of adaptive signal processing in the nervous system are likely to require a mechanism for gain control at the single neuron level. To properly adjust the gain of an individual neuron, it may be necessary to use information carried by neurons in other parts of the system. The ability to adjust the gain of neurons in one part of the brain, using control signals arising from another, has been observed in the electrosensory system of weakly electric fish, where descending pathways to a first-order sensory nucleus have been shown to influence the gain of its output neurons. Although the neural circuitry associated with this system is well studied, the exact nature of the gain control mechanism is not fully understood. In this paper, we propose a mechanism based on the regulation of total membrane conductance via synaptic activity on descending pathways. Using a simple neural model, we show how the activity levels of paired excitatory and inhibitory control pathways can regulate the gain and baseline excitation of a target neuron.
Exploring the Emergence of Side Biases and Familiarity–Novelty Preferences from the Real‐Time Dynamics of Infant Looking

This study examined how look dynamics contribute to infants’ emerging novelty preferences. Time-series analyses were used to study the temporal nature of looking displayed by 3- to 5-month-old infants during a serial paired-comparison task. Evidence was found only for short-term stability: Novelty preferences and side biases were not stable from one visit to the next, but looking was consistent from one moment to the next producing stability within trials and temporarily across trials leading to the formation of behavioral runs. Persistence in looking left or right across multiple trials did not change from one visit to the next, but persistence in looking at familiar stimuli declined with age. By Visit 3, familiarity runs occurred less often than did novelty runs. Frequent but highly variable runs, including surprisingly late familiarity preferences, suggest that overall side biases and novelty preferences found during visual preference tasks are emergent phenomena affected by moment-to-moment changes in looking.
Potential use of an antagonist of cAMP‐dependent protein kinase to block inhibition and modulate T‐cell receptor‐triggered activation of cytotoxic T‐lymphocytes

It was recently established that cAMP-dependent protein kinase (PK-A) inhibits both early and late stages of T-cell receptor-mediated cytotoxic T-lymphocyte (CTL) activation. We suggested that PK-A may function as a part of a biochemical down-regulating “off” signal in regulation of CTL activities. It is proposed here to use antagonists of PK-A to block such an inhibitory pathway, thereby enhancing immune response. We explored this possibility using the diastereomer of adenosine cyclic 3′,5′-phosphorothioate (Rp-cAMPS), a recently described PK-A antagonist. It is shown that Rp-cAMPS blocks cAMP-induced inhibition of lytic activity and of exocytosis of granules from CTL. The immunomodulating potential of cAMP analogues which inhibit PK-A is discussed.
Quantitative Description of Signaling Downstream of Gq-Coupled Receptors: Similarities and Differences in the Responses of IP3, Calcium, DAG, PKC, and PIP2

Gq-coupled plasma membrane receptors modulate cellular functions by activating phospholipase C (PLC), which hydrolyses the membrane lipid phosphatidylinositol (4,5)-bisphosphate (PIP2) into the second messengers inositoltrisphosphate (IP3) and diacylgycerol (DAG). To better understand the mechanisms that govern these partially independent signals we monitored in single, living tsA-201 cells levels of PIP2, IP3, calcium, DAG, and PKC by optical probes and current. We compared (i) activation of (low-abundance) endogenous purinergic receptors and overexpressed M1 muscarinic receptors, and (ii) different concentrations of the muscarinic agonist oxotremorine-M (oxo-M). Whereas the peak responses from reporters of IP3 (LIBRAvIII) and DAG (C1 domains of PKCγ) scale with abundance of receptor or agonist, downstream production of calcium (Fura4F) and PKC activation (CKAR) do not. Amplitude and duration of calcium signals elicited by 100 µM UTP, 10 nM oxo-M, or 10 µM oxo-M are almost identical. The only difference is a shorter latency with 10 µM oxo-M. These data suggest that a relatively low amount of IP3 is required for calcium release. This interpretation is supported by the finding that a full-size calcium response can still be elicited after PIP2 is depleted by recruiting a PI 5-phosphatase to the plasma membrane (by rapamycin-induced dimerization). Duration and late recovery time courses are different between IP3 (duration=68 s; τoff =55 s) and calcium (duration=110 s; τoff =34 s), suggesting that once a threshold of IP3 is reached, the calcium signal unfolds. Therefore we conclude that the IP3 requirement for calcium release must be low. The time point and IP3 level (from LIBRAvIII) at which the calcium response starts can provide an estimate of this IP3 threshold. Supported by NIH grants NS08174 & GM83913 and the HFSP.
Embolization: An adjunctive measure for removal of carotid body tumors†

Small carotid body tumors that do not encircle the internal carotid artery are excised with relative ease and minimal risk by the conventional subadventicial approach. Large carotid body tumors frequently encircle the internal and external carotid arteries, and extensive bleeding often complicates the resection, increasing the risk of carotid artery rupture and damage to major cranial nerves. Recent improvements in surgical techniques and selective embolization have lessened the risks of surgical excision, decreased the blood loss, and diminished the time required for resection. Experiences in the resection of carotid tumors with and without embolization are compared. Early resection of carotid body tumors, before involvement of the internal carotid artery and carotid bulb, is advocated.
Spectral characteristics of the P codas of Eurasian earthquakes and explosions

Abstract Spectral analysis of “infinite velocity sum” subarray beams at LASA for the P codas of 36 explosions and 23 earthquakes indicates the presence of 6 to 9 Hz energy well above noise level for large explosions and earthquakes. A discriminant ( D ), based on use of the full spectral bandwidth from 0.4 to 9 Hz, successfully discriminates all Eurasian explosions and shallow-focus earthquakes. The basic character and contrast in spectral composition of the source spectra of earthquakes and explosions is discussed. It is pointed out that the discriminant ( D ), when use is made of signals recorded in the range 60° to 90°, is as or more successful in discriminating events of near m b 4.0 as those at and above m b 6.0, and the basis for this success is clarified. It is suggested that proper use of P coda spectral discriminants appears capable of achieving identification essentially at the detection threshold of a network, while circumventing such problems as refined depths of focus, mixed events, etc.
Studies on ribosomal mutants of Salmonella typhimurium LT-2.

Mutations conferring resistance to spectinomycin, resistance to neomycinkanamycin and cold-sensitivity of ribosome biosynthesis were located on the Salmonella typhimurium chromosome in relation to the genes cysG, strA, and aroC. The effect of temperature and growth medium on the expression of these mutations, and the interactions between the mutations was determined as a prerequisite to the mapping. On the basis of chromosomal location and dominance, it is concluded that cold-sensitivity of ribosome synthesis can result from mutations in several distinct genes.
Backscattering enhancement of light by nanoparticles positioned in localized optical intensity peaks

We report what we believe to be a novel backscattering phenomenon associated with localized optical intensity peaks (spanning as little as 43 nm) arising at the shadow-side surfaces of plane-wave-illuminated dielectric microcylinders of noncircular cross sections. Namely, for nanometer-scale dielectric particles positioned within the localized intensity peaks, their backscattering of visible light is enhanced by several orders of magnitude relative to the case of isolated nanoparticles (i.e., Rayleigh scattering). The positions of the localized intensity peaks can be quickly scanned along the microcylinder surface by changing either the incident wavelength or angle. This combination of giant backscattering enhancement of nanoparticles and ease and rapidity of scanning may present advantages relative to the use of fragile, mechanically scanned, near-field probes. Potential applications include visible-light detection, characterization, and manipulation of nanoparticles.
Localized CO 2 -laser treatment for mitigation of 351-nm damage growth in fused silica

A technique for inhibiting the growth of laser-induced surface damage on fused silica, initiated and propagated at the 351-nm laser wavelength, has been investigated. The technique exposes the damage sites to single pulses of a CO2 laser operating at the 10.6 micrometers wavelength at or near beam focus. This method results in a very localized treatment of the laser damage site and modifies the site such that laser damage does not propagate further. A laser damage site initiated with a single pulse of 355-nm laser light at approximately 45 J cm-2 and 7.5-ns pulse duration grows rapidly upon further illumination at 8 J cm-2 with 100% probability. Treatment of these sites with single pulses of 10.6 micrometers laser light for one second at a power level of between 17 and 37 Watts with a beam diameter of 5 mm alters the damage site such that it does not grow with subsequent 351-nm laser illumination at 8 J cm-2 10-ns pulse duration for > 1000 shots. The technique has been found to be 100% effective at stopping the growth of the laser damage.
Finite Element Analysis on the Random Chopped Fiber Composites

A micro-mechanics based finite element analysis method for random chopped fiber composites is applied. A modified random sequential adsorption technique is developed to generate representative volume elements of the composites so to overcome the “jamming limit” in the existing techniques. A homogenization scheme is applied to acquire the effective elastic constants of the composite. Two damage mechanisms are considered, matrix cracking and interfacial debonding, which occur prior to fiber breakage and consequentially leading to catastrophic failure. The incremental plastic model and the cohesive zone model are adopted to account for matrix plasticity and interfacial debonding, respectively. The finite element analysis results are validated by experimental data.Copyright © 2009 by ASME
Prediction of Thermal Contact Conductance in Vacuum by Statistical Mechanics

Despite substantial theoretical studies of thermal contact conductance in the past, the application of statistical mechanics in this field has never been attempted. We address contact conductance from macroscopic and microscopic viewpoints in order to demonstrate the promise of the statistical mechanics approach. In the first part of the derivation, the Boltzmann statistical model is applied to determine the most probable distribution of asperity heights for a homogeneously, isotropically rough surface. The result found is equivalent to Gaussian distribution, which has only been assumed but not rigorously substantiated in the past. Subsequently, the Boltzmann statistical model is applied to predict the distribution of true contact spots when two such surfaces are pressed together, resulting in a relationship between the total thermal contact conductance and the relative interfacial pressure
Amorphization of Indomethacin by Co-Grinding with Neusilin US2: amorphization kinetics, physical stability and mechanism.

To quantify the effects of the ratio of indomethacin to Neusilin US2 and the processing humidity on the amorphization kinetics, stability and nature of the interaction. A porcelain jar mill with zirconia balls was used to affect conversion of the physical mixtures (48 g) of indomethacin and Neusilin US2 (in the ratios 1:1 to 1:5) to amorphous states at room temperature (25°C) employing either 0% RH or 75% RH. The percent crystallinity in the samples was determined from ATR-FTIR scans chemometrically. The physical stability of these co-ground amorphous powders was evaluated at 40°C/75% RH and 40°C/0% RH. The lower the ratio of indomethacin to Neusilin US2, the faster is the amorphization during co-grinding. Higher humidity facilitates amorphization with a more pronounced effect at the lower ratio of indomethacin to Neusilin US2. There is further amorphization of some of the partially amorphized samples on storage at 40°C/75% RH for 3 months. Hydrogen bonding and surface interaction between metal ions of Neusilin US2 and indomethacin can explain changes in the FTIR spectra. The processing humidity and the ratio of indomethacin to Neusilin US2 are important factors to be considered to affect amorphization during ball milling. Amorphous indomethacin can be stabilized by co-grinding with Neusilin US2.
The de novo design and synthesis of cyclic urea inhibitors of factor Xa: Initial sar studies

Abstract In this report we discuss the design, synthesis, and validation of a novel series of cyclic urea inhibitors of the blood coagulation protein Factor Xa. This work culminates in compound 11 , a mono-amidine inhibitor of fXa employing a new S4 ligand that reduces the cationic character of these analogs. Compound 11 represents a lead for a series of more potent and selective inhibitors.
Molecular Determinants for the Genesis of the Action Potential

In nerves and muscles, action potentials are initiated by the rapid activation of voltage-gated sodium (Nav) channels and terminated by the delayed activation of voltage-gated potassium (Kv) channels. This sequential activation, which is the prerequisite for the genesis of the action potential, requires faster activation kinetics of the voltage-sensor domains (VSD) in Nav as compared to Kv channels. Despite on decades of investigations, the molecular determinants and mechanisms underlying this phenomenon remain elusive. Here, we show that this differential gating is mostly imparted by six conserved hydrophilic residues Thr or Ser located in the S2 and S4 segments of the VSD in domains I-III of Nav channels while these positions are commonly occupied by hydrophobic residues in the VSD of Kv channels. Hydrophilic substitutions at the S2 position in the Shaker Kv channel accelerate the gating charge transfer by decreasing its energy barrier while hydrophilic substitutions at the S4 position speed up VSD activation by destabilizing its resting conformation. Interestingly, these hydrophilic residues are present in a Nav-related gene expressed in an evolutionary-distant unicellular choanoflagellate, suggesting that rapidly-gated Nav channels evolved before the emergence of metazoans and their nervous systems. We also show that the physiological co-expression of the ubiquitous regulatory β1 subunit further accelerates VSD movement in both a neuronal and a muscular Nav, providing a molecular basis for the β1-dependent fast gating mode previously detected from the ionic conductance. Our study uncovers the fundamental molecular determinants and possible mechanisms that enabled the differential gating in sodium and potassium channels and the emergence of the action potential. This work was supported by NIH grant GM030376.
Failure of Premature Rabbits to Increase Antioxidant Enzymes During Hyperoxic Exposure: Increased Susceptibility to Pulmonary Oxygen Toxicity Compared with Term Rabbits

ABSTRACT: Although the prematurely born are known to have decreased baseline levels of protective antioxidant enzymes (Frank L, Sosenko IRS: J Pediatr 110:9 and 106, 1987), the ability to augment the baseline values during high O2 exposure is the key factor determining O2 tolerance versus O2 susceptibility. We have compared the pulmonary antioxidant enzyme responses of prematurely delivered rabbits (gestational d 29 of 32) and full-term rabbits to 48–72 h of hyperoxic exposure. We found that although full-term newborns exposed to >90% O2 consistently showed elevated superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase activities, the premature animals repeatedly failed to respond to hyperoxia with increased antioxidant enzyme activity levels. Consistent with the comparative antioxidant enzyme responses were the evidences of O2 toxicity in the two age groups. The prematurely born rabbits had significantly increased lung lavage protein content, lung conjugated diene levels, and more severe light microscopic lung pathology compared with the full-term animals during equal O2 exposure time. This first reported comparison of prematurely born versus full-term animal responses to hyperoxia might help to explain the clinical observation that the very prematurely born infant is excessively prone to the development of O2-induced lung injury and the progressive development of bronchopulmonary dysplasia.
Do social networking technologies have a place in formal learning environments

Purpose – This viewpoint essay seeks to discuss the promise and perils of integrating social networking technologies into formal learning environments.Design/methodology/approach – The work is grounded in a new literacies perspective and brings insights from learning in participatory cultures to bear in the discussion of social networking sites in formal settings.Findings – The paper describes three major design trade‐offs in the use of social networking sites: privacy versus redundancy when participating in an SNS; whether goals for participation are endogenous or exogenous learning goals; and conception of identity in SNSs as holistic versus identity in formal learning environments as uniquely constructed in the learning setting.Practical implications – These design trade‐offs arise as a result of importing technologies for learners into environments that are better suited to technologies for learning. Therefore, the paper suggests that the goals for learning are more important than the use of any indiv...
Thymic function and allogeneic T-cell responses in stem-cell transplantation.

Summary The thymus is the primary site of T-cell production early in life, and has now been shown to continue to function in both healthy and immunocompromised individuals late into life. Positive and negative selection occurring in the thymus are two of the most important processes that govern the development and specificity of peripheral T cells, including their restriction to self HLA and their ability to respond in an alloreactive manner. In the chimeric state that follows successful allogeneic stem-cell transplants, the specificity of alloreactive cells may be governed by either host- or recipient-derived cellular elements, as well as maturing lymphoid cells, which are, in turn, derived from donor stem cells or host cells surviving transplant conditioning. The ability to measure recent thymic emigrants via the detection of T-cell receptor excision circles has facilitated studies of thymic function in immunodeficient individuals, including HIV-1 infected subjects and recipients of autologous or allogeneic stem-cell transplant (SCT). These studies have now demonstrated that thymic function is likely to play a beneficial role in immune reconstitution in these settings, but have yet to clearly demonstrate what clinical variables are the most important determinants of thymic persistence. It is also not yet clear how much the degree of thymic function following allogeneic SCT influences the alloreactive T-cell repertoire, although studies in animal models and early clinical studies suggest that GvHD results in thymic injury and dysfunction. Future studies will further clarify how thymic function shapes the repertoire of T cells that mediate alloreactivity, as well as protective pathogen-specific immune responses, following SCT. Finally, these studies will also demonstrate whether endogenous mediators of thymic function could be selectively applied to regulate post-SCT thymic function and alloreactivity.
CAT : A TOOL FOR ELICITING KNOWLEDGE ON HOW TO PERFORM PROCEDURES

Procedural tasks involve context-sensitive sequences of actions that are performed in pursuit of goals. Procedural knowledge specifies how to do something (e.g., repairing a car) but not how the physical system works (e.g., how the engine works). We have developed a computer program that elicits procedural knowledge from individuals with varying amounts of domain knowledge (ranging from novices to experts) and varying amounts of computer literacy. The tool is called CAT (cognitive analysis tool). CAT is an extension of a class of cognitive models known as GOMS, which stands for goals, operators, methods, and selection rules. The tool guides the user in articulating the goals (and subgoals) the user wants to accomplish, the operators (actions, steps) to accomplish each goal, the alternative methods of accomplishing goals, the conditions in which each method is applied, and exceptional circumstances when goals are suspended and restarted. CAT can be used on most IBMcompatible microcomputers.
Molecular Genetics and Pathogenesis of Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is a common and systemic disease characterized by formation of focal cysts. Of the three potential causes of cysts, downstream obstruction, compositional changes in extracellular matrix, and proliferation of partially dedifferentiated cells, evidence strongly supports the latter as the primary abnormality. In the vast majority of cases, the disease is caused by mutations in PKD1 or PKD2, and appears to be recessive at the cellular level. Somatic second hits in the normal allele of cells containing the germ line mutation initiate or accelerate formation of cysts. The intrinsically high frequency of somatic second hits in epithelia appears to be sufficient to explain the frequent occurrence of somatic second hits in the disease-causing genes. PKD1 and PKD2 encode a putative adhesive/ion channel regulatory protein and an ion channel, respectively. The two proteins interact directly in vitro. Their cellular and subcellular localization suggest that they may also function independently in a common signaling pathway that may involve the membrane skeleton and that links cell-cell and cell-matrix adhesion to the development of cell polarity.
Effects of excitation rise-time and charge injection conditions on the transient field and charge behavior for unipolar conduction

Abstract Recent analysis using a unipolar ion mobility conduction model is continued and extended by taking into account the experimental realities of excitation rise-time and charge injection threshold conditions. The transient behavior of the bulk electric field and space charge distributions as a function of time and position as well as the resulting time dependence of the terminal voltage and current are found for an imposed voltage or current excitation with non-zero rise-time, contrasting the behavior between field or charge specification at the emitter electrode with charge injection onset once the emitter electric field exceeds a threshold value. Representative plots of field and charge distributions as well as voltage and current time dependence for various excitations, rise-times, and boundary conditions are presented. Important time constants which can be correlated to experiments under these various conditions are tabulated and where possible, results are presented in closed form.
Ion channel focusing in FEL wigglers

Accumulation of ions inside FEL (free electron laser) wigglers can significantly alter electron beam transport and lead to a reduction of laser gain. This is of particular importance to devices driven by RF accelerators with continuous operation and with long wigglers. It is shown that while the mechanism for ion channel formation is the same as in electron beam storage rings, the problem appears less severe because the electron beam makes only a single pass through the system. In addition, the electric field of the beam together with the magnetic field of the wiggler causes an E*B drift, which can provide an effective mechanism for ion removal. >
Broadband modelling of regional seismograms: Imperial Valley to Pasadena

SUMMARY This paper addresses broadband wave propagation along a corridor from Imperial Valley to Pasadena, California. The path consists of 50 km of slow basin structure with a shallow Moho followed by 250 km of relatively normal southern California structure approaching Pasadena. Events occurring in the valley produce extended body wave codas which carry a dispersive waveform imprint along with longer period Rayleigh waves. Many features of these seismograms at periods greater than a few seconds can be modelled by applying a finite-difference technique to a 2-D structure. Shorter periods display complex behaviours not easily modelled by present techniques, especially for shallow events. Events occurring in the normal structure produce broadband SH-waveforms that can be modelled, analytically, if some extra empirically derived alignment parameters determined from calibration events are used. These parameters are determined by adjusting traveltime differentials between the decomposed wavefield S, sS, etc. For example, delays in sS relative to S correspond to local corrections for sediment cover for a particular source region. Source complexity such as asperities and directivity become increasingly important at shorter periods, as demonstrated by numerical experiments and observation.
Size reduction using Mirror Visual Feedback (MVF) reduces phantom pain.

Following limb amputation patients continue to feel the vivid presence of a phantom limb. A majority of patients also experience pain in the phantom and sometimes (as in our case DS) the pain is severe. Remarkably we find that optically ‘resurrecting’ the phantom with a mirror and using a lens to make the phantom appear to shrink caused the pain to ‘shrink’ as well.
Markers of intestinal inflammation in patients with ankylosing spondylitis: a pilot study

Inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) are similar chronic inflammatory diseases whose definitive etiology is unknown. Following recent clinical and genetic evidence supporting an intertwined pathogenic relationship, we conducted a pilot study to measure fecal calprotectin (fCAL) and IBD-related serologies in AS patients. Consecutive AS patients were recruited from a long-term prospectively collected longitudinal AS cohort at Cedars-Sinai Medical Center. Controls were recruited from Cedars-Sinai Medical Center employees or spouses of patients with AS. Sera were tested by ELISA for IBD-associated serologies (antineutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibody IgG and IgA, anti-I2, anti-OmpC, and anti-CBir1). The Bath Ankylosing Spondylitis Disease Activity Index, the Bath Ankylosing Spondylitis Functional Index, and the Bath Ankylosing Spondylitis Radiology Index were completed for AS patients. A total of 81 subjects (39 AS patients and 42 controls) were included for analysis. The average age of AS patients was 47 years and the average disease duration was 22 years. AS patients were predominantly male; 76% were HLA-B27-positive. Median fCAL levels were 42 μg/g and 17 μg/g in the AS group and controls, respectively (P < 0.001). When using the manufacturer's recommended cutoff value for positivity of 50 μg/g, stool samples of 41% of AS patients and 10% of controls were positive for fCAL (P = 0.0016). With the exception of ANCA, there were no significant differences in antibody levels between patients and controls. Median ANCA was 6.9 ELISA units in AS patients and 4.3 ELISA units in the controls. Among AS patients stratified by fCAL level, there were statistically significant differences between patients and controls for multiple IBD-associated antibodies. Calprotectin levels were elevated in 41% of patients with AS with a cutoff value for positivity of 50 μg/g. fCAL-positive AS patients displayed higher medians of most IBD-specific antibodies when compared with healthy controls or fCAL-negative AS patients. Further studies are needed to determine whether fCAL can be used to identify and characterize a subgroup of AS patients whose disease might be driven by subclinical bowel inflammation.
Candidate Genetic Variants in the Fibrinogen, Methylenetetrahydrofolate Reductase and Intercellular Adhesion Molecule-1 Genes and Plasma levels of Fibrinogen, Homocysteine, and Intercellular Adhesion Molecule-1 Among Various Race/ethnic Groups: Data from the Women’s Genome Health Study

Background Although inflammation is a core element of atherogenesis and plasma levels of fibrinogen (FGB), homocysteine, and intercellular adhesion molecule-1 (ICAM-1) differ by race/ethnicity, little is known about the role of genetic polymorphisms in the FGB, methylenetetrahydrofolate reductase (MTHFR), and ICAM-1 genes in determining plasma levels of these biomarkers. We examined the relationship between specific polymorphisms in the FGB, homocysteine, and ICAM-1 genes and their respective inflammatory biomarker concentrations at baseline in women from different race/ethnic groups. Methods We genotyped specific polymorphisms in FGB (−455G>A/rs1800790), MTHFR (677C>T/rs1801133), and ICAM-1 (Lys56Met/rs5491 and Gly241Arg/rs1799969) at baseline and evaluated their relationship with respective inflammatory biomarker levels in 25,565 white, 476 African-American (black), 277 Hispanic, and 370 Asian women participating in the Women's Genome Health Study. Results Overall, the minor allele frequencies for −455G>A were similar among white, Hispanic, and Asian women (17.2%-21.9%) but significantly lower in black women (6.6%, P T polymorphism was lowest in blacks (blacks 12.1%, whites 33.1%, Hispanics 39.0%, Asians 24.0%), and the T allele was only significantly associated with homocysteine levels in white women. Among whites, Hispanics, and Asians, the Lys56Met polymorphism was rare compared to the frequency in blacks ( P Conclusion We found significant associations between certain candidate genetic polymorphisms and baseline plasma levels of FGB, homocysteine, and ICAM-1 in women from various race/ethnic groups. The present investigation is hypothesis generating and suggests genetic determination of differential concentrations of these atherosclerosis-related inflammatory biomarkers differ among various race/ethnic groups.
Vav2 protein overexpression marks and may predict the aggressive subtype of ductal carcinoma in situ

A subset of patients with ductal carcinoma in situ (DCIS) will develop invasive breast cancer (IBC). To date, there are no effective predictive biomarkers for identifying this subset with worse prognosis whose lesions are essentially indistinguishable histologically from those with favorable outcomes. We hypothesized that measurable parameters that discriminate DCIS from DCIS with concurrent invasion may serve as diagnostic biomarkers (BM) of progressive cancer in situ (CIS). Using a novel imaging-based method of tissue testing, we measured the relative expression levels of three candidate BM proteins specifically implicated in IBC progression - the insulin-like growth factor I receptor (IGF-IR), Ras-related protein 1 (Rap1), and Vav2 oncoprotein. Protein profiles were compared in 42 histologically normal mammary epithelial samples, 71 CIS (35 without/36 with invasion either on diagnostic biopsy or final surgical excision), and 98 IBC of known estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. The levels of the IGF-IR and Rap1 protein expression were significantly elevated in ER-positive (ER+/PR+/-/HER2 –) DCIS relative to normal epithelium (P <0.0001). The IGF-IR protein expression was also significantly up regulated in HER2-positive (ER+/-/PR+/-/HER2+) DCIS relative to normal epithelium (P = 0.0002). IGF-IR and Rap1 protein expression levels were similar among DCIS patients without or with concurrent invasion. Vav2 upregulation in DCIS relative to normal group was not associated with steroid hormone receptor and HER2 status, but was associated with the presence of concurrent invasion, including microinvasion (invasive foci of less than 1 mm). DCIS with high Vav2 were more than twice as likely to progress to invasive cancers as DCIS with low Vav2 (odds ratio, 2.42; 95% CI, 1.26-4-65; P =0.008). Furthermore, a receiver operating characteristic curve analysis revealed moderate ability of Vav2 protein expression measurements in DCIS to predict the existence of invasion concurrent with DCIS (area under the curve, 0.71; 95% CI, 0.59- 0.84). Our novel findings hold promise for utilizing Vav2 protein as a predictive BM for differentiating progressive from non-progressive DCIS.
Intraesophageal Administration of GS-Nitroxide (JP4-039) and p53/MDM2/MDM4 Inhibitor (BEB55) Ameliorates Radiation Esophagitis

 The goal of this project was to determine whether GS-nitroxide (JP4-039) and the p53/MDM2/MDM4 inhibitor (BEB55) may be able to protect against radiation induced esophagitis. Figure 2. Improved survival after thoracic irradiation by orally administered BEB55. Mice were injected with BEB55 intraesophageally prior to A: 29 Gy thoracic irradiation, or B: each of 4 daily fractions of 11.5 Gy thoracic irradiation. Mice that received BEB55 or MnSOD-PL prior to irradiation demonstrated increased survival compared to the vehicle control group in both singleand multiple-fraction administration.
Acute Alcohol Exposure Exerts Anti-Inflammatory Effects by Inhibiting IκB Kinase Activity and p65 Phosphorylation in Human Monocytes

Acute alcohol use is associated with impaired immune responses and decreased proinflammatory cytokine production. Our earlier studies have shown that acute alcohol intake inhibits NF-kappaB DNA binding in an IkappaBalpha-independent manner. We report using human peripheral blood monocytes and Chinese hamster ovary cells transfected with CD14 cells that acute alcohol treatment in vitro exerts NF-kappaB inhibition by disrupting phosphorylation of p65. Immunoprecipitation of p65 and IkappaBalpha revealed that acute alcohol exposure for 1 h decreased NF-kappaB-IkappaBalpha complexes in the cytoplasm. Phosphorylation of p65 at Ser(536) is mediated by IkappaB kinase (IKK)beta and is required for NF-kappaB-dependent cellular responses. We show that acute alcohol treatment decreased LPS-induced IKKalpha and IKKbeta activity resulting in decreased phosphorylation of p65 at Ser(536). Furthermore, nuclear expression of IKKalpha increased after alcohol treatment, which may contribute to inhibition of NF-kappaB. Decreased phosphorylation of nuclear p65 at Ser(276) was likely not due to alcohol-induced inhibition of protein kinase A and mitogen- and stress-activated protein kinase-1 activity. Although decreased IkappaBalpha phosphorylation after acute alcohol treatment was attributable to reduced IKKbeta activity, degradation of IkappaBalpha during alcohol exposure was IKKbeta-independent. Alcohol-induced degradation of IkappaBalpha in the presence of a 26S proteasome inhibitor suggested proteasome-independent IkappaBalpha degradation. Collectively, our studies suggest that acute alcohol exposure modulates IkappaBalpha-independent NF-kappaB activity primarily by affecting phosphorylation of p65. These findings further implicate an important role for IKKbeta in the acute effects of alcohol in immune cells.
Thermal-aware test scheduling and hot spot temperature minimization for core-based systems

Chip overheating has become a critical problem during test of today's complex core-based systems. In this paper, we address the overheating problem by incorporating thermal constraints in the test scheduling of core-based systems. We propose two algorithms for which the objective is to spread heat more evenly over the chip and reduce hot spots. The first uses the layout information to guide test scheduling, while the second relies on a progressive weighting mechanism. Experimental results show that the proposed thermal-constrained methods can not only guarantee a thermal-safe test schedule, but also reduce hot spot temperatures, leading to a balanced thermal distribution across the chip during test.