cssi/SciSciGPT-SciSciNet huggingface dataset:
Competing methyltransferase systems.

Abstract Large differences between the transfer RNA methyl-transferase capacity of adult organs and their fetal counterparts, as well as between tumor tissues and normal tissues, have been observed. This is in part due to the presence of natural inhibitors of the tRNA methyltransferases in normal adult tissues. An inhibitory system present in the liver, kidney, and pancreas of adult rabbit and rat has been identified. The inhibitory effect of extracts of these organs on the tRNA methyltransferases is due to the presence of an enzyme which methylates glycine to yield sarcosine and S-adenosylhomocysteine (S-adenosylmethionine: glycine N-methyltransferase). The glycine methyltransferase not only competes with the tRNA methyltransferases for the methyl donor S-adenosylmethionine but its product S-adenosylhomocysteine is a potent inhibitor of the tRNA methyltransferases and a relatively weak inhibitor of the glycine methyltransferase. The glycine methyltransferase is found only in those organs where elevated levels of S-adenosylmethionine-synthesizing enzyme have been observed. It is present at either very low levels or not at all in fetal organs and several tumor tissues. It is postulated that the glycine methyltransferase serves a role in regulating the relative levels of S-adenosylmethionine and S-adenosylhomocysteine, thus exerting some control over those methyltransferases whose activity is more sensitive to the action of S-adenosylhomocysteine.
Cor triatriatum. Successful diagnosis and surgical correction in a three year old girl.

Abstract Successful diagnosis and surgical repair of a cor triatriatum defect (stenosis of common pulmonary vein) in a three year old girl is described. Prior to surgery severe pulmonary hypertension was found at right heart catheterization, with a mean pulmonary artery wedge pressure of 35 mm. Hg. Nine months after surgery there was a normal mean pulmonary artery wedge pressure of 6 mm. Hg. Except for a transient but severe episode of cardiac failure in the immediate postoperative period, the patient showed an excellent response to surgery. This case illustrates the typical clinical features of cor triatriatum as seen in young children. The symptoms and signs are those of pulmonary venous and arterial hypertension, and are related to the size of the stenotic orifice. Dyspnea is a central feature in persons of all ages. The majority of patients die within the first two years of life, often after a relatively short period of symptoms. In such cases differentiation from congenital mitral stenosis, endocardial fibroelastosis, anomalous pulmonary venous connection or primary pulmonary disease may be difficult. However, at any age, clinical evidence of pulmonary hypertension and the finding of an elevated pulmonary artery wedge pressure are highly suggestive; and if associated with normal left atrial pressure, are pathognomonic for this anomaly. Although comparatively rare, cor triatriatum is easily and completely corrected by surgery and therefore deserves particular emphasis. Surgical exploration for this defect is justified in patients with high pulmonary artery wedge pressure and near normal size of the left atrium.
Time dependent transportation network models

Network data models are frequently used as a mechanism to solve wide range of problems typical for the GIS applications and transportation planning in particular. They do this by modelling the two most important aspects of such systems: the connectivity and the attribution. For a long time the attributes like the travel time, associated with a transportation network model have been considered static. With the advancement of the technology data vendors now have the capability to capture more accurate information about the speeds of streets at different times of the day and provide this data to customers. The network attributes are not static anymore but associated with a particular time instance (e.g time-dependent). In this paper we describe our time dependent network model tailored towards the need of transportation network modelling. Our solution is based on the existing database functionality (tables, joins, sorting algorithms) provided by a standard relational DBMS and has been implemented and tested and currently being shipped as a part of the ESRI ArcGIS 10.1 platform and all subsequent releases.
High Performance Sparse LU Solver FPGA Accelerator Using a Static Synchronous Data Flow Model

Sparse LU solvers are common in several scientific problems. The hardware utilization of previous implementations on massively parallel platforms never exceeded the 20% mark (including multicores, GPU, and FPGA). This is due to the highly irregular computation and memory access pattern of the algorithm. Reconfigurable fabrics, with its spatial execution model, can expose the maximum inherent parallelism in the problem and achieve the highest hardware utilization. However, dynamic data flow models implementations suffer from large overhead and scalability issues. In this paper, we propose a static dataflow synchronous model that maximizes the utilization of FPGA-based architectures. Synchronous dataflow graph is mapped to a mesh of deeply-pipelined PEs to perform the factorization. This inspires the development of a customized data structure format that reduces memory accesses, indexing overhead and pipelining hazards. The hardware model is synthesized on a VIRTEX 7 FPGA and the results show a hardware utilization exceeding 60%, which was translated to more than 100 GFLOPS.
FPGA-Based true random number generation using circuit metastability with adaptive feedback control

The paper presents a novel and efficient method to generate true random numbers on FPGAs by inducing metastability in bi-stable circuit elements, e.g. flip-flops. Metastability is achieved by using precise programmable delay lines (PDL) that accurately equalize the signal arrival times to flip-flops. The PDLs are capable of adjusting signal propagation delays with resolutions higher than fractions of a pico second. In addition, a real time monitoring system is utilized to assure a high degree of randomness in the generated output bits, resilience against fluctuations in environmental conditions, as well as robustness against active adversarial attacks. The monitoring system employs a feedback loop that actively monitors the probability of output bits; as soon as any bias is observed in probabilities, it adjusts the delay through PDLs to return to the metastable operation region. Implementation on Xilinx Virtex 5 FPGAs and results of NIST randomness tests show the effectiveness of our approach.
Cell Density and N-Cadherin Interactions Regulate Cell Proliferation in the Sensory Epithelia of the Inner Ear

Sensory hair cells in the inner ears of nonmammalian vertebrates can regenerate after injury. In many species, replacement hair cells are produced by the proliferation of epithelial supporting cells. Thus, the ability of supporting cells to undergo renewed proliferation is a key determinant of regenerative ability. The present study used cultures of isolated inner ear sensory epithelia to identify cellular signals that regulate supporting cell proliferation. Small pieces of sensory epithelia from the chicken utricle were cultured in glass microwells. Under those conditions, cell proliferation was inversely related to local cell density. The signaling molecules N-cadherin, beta-catenin, and focal adhesion kinase were immunolocalized in the cultured epithelial cells, and high levels of phosphotyrosine immunoreactivity were present at cell-cell junctions and focal contacts of proliferating cells. Binding of microbeads coated with a function-blocking antibody to N-cadherin inhibited ongoing proliferation. The growth of epithelial cells was also affected by the density of extracellular matrix molecules. The results suggest that cell density, cell-cell contact, and the composition of the extracellular matrix may be critical influences on the regulation of sensory regeneration in the inner ear.
Due Process in the American Identity

In the last four years, public opinion polls have found an increasingly high level of public support for the methods applied in the war on terror. A significant majority of the population now expresses support for targeted killing through drone strikes and for the indefinite detention of suspected terrorists at Guantanamo Bay. While there are undoubtedly many dynamics at play in the public’s changing views of national security and due process, this Article examines one piece of the puzzle: how the concept of due process fits within the structure of the American identity.This Article examines due process and national security through the lens of social psychology, and its approach helps to shed light on how and why public opinion has changed. It opens by contrasting the doctrinal view of due process as a legal principle with an opposing view of due process as an expression of American values, and it concludes that both views can give rise to similar policy choices — but for fundamentally different reasons. The Article then applies two related theories from social psychology to explore how people’s views of due process interact with their national identity to create support for different policy choices. Finally, it argues that separating these strands in the public debate on the war on terror can facilitate the conscious consideration of our national identity. In turn, this explicit recognition of the intertwining of identity and policy can create the opportunity to intentionally shape national identity. In order to do so, however, we must broaden the discussion beyond the legality of national security policies — or even their instrumental value — and move the discussion into an examination of more fundamental questions of who we are as a nation and who we want to be.
Friction, Wear, and Aging of an Alkoxy-monolayer Boundary Lubricant on Silicon

We study the friction, wear, and aging of a model boundary lubricant, an alkoxy monolayer covalently bonded to a Si(111) surface, using an interfacial force microscope with a spherical diamond probe. The robust alkoxy bond creates a film that effectively lubricates and prevents wear of Si at stresses comparable to those found in microelectromechanical systems devices. Sliding on the monolayer over 50 nm produced friction approximately three times greater than that of sliding over molecular length scales (∼2 nm); this is attributed to deformation dynamics of the experiment. By repeated scanning over the same location, we observed wear on a level that reduces the friction by thinning and/or reordering the monolayer film.
Adsorption of weak polyelectrolytes on metal oxide surfaces : A hybrid SC/SF approach

A hybrid SC/SF model to describe the adsorption of weak polyelectrolytes on metal oxide surfaces is presented. This model couples the surface complexation (SC) model for the effects of surface and solute speciation on the adsorption of monomers on oxides with the Scheutjens−Fleer (SF) model for the effects of macromolecular properties on the adsorption of polymers and polyelectrolytes on surfaces. The average magnitude of the specific interactions between polyelectrolyte functional groups and surface sites, expressed by the parameter χs(hyb), varies systematically with surface and polyelectrolyte speciation and hence with solution chemistry. Measurements of the adsorption of polygalacturonic acid (PGUA) on hematite over wide ranges of pH and ionic strength are used to test the hybrid model. Good agreement of model simulations and adsorption measurements is achieved. A reaction represented by >MeOH + L- = >MeOHL- provides the best representation of the experimental data.
Thermoradiotherapy for residual microscopic cancer: elective or post-excisional hyperthermia and radiation therapy in the management of local-regional recurrent breast cancer

Abstract A Phase I/11 study was undertaken to investigate the efficacy and side effects of combined hyperthermia and radiation therapy in the management of presumed or known microscopic residual tumors. Between February 1985 and March 1991, 262 fields in 89 patients with local-regional recurrent breast cancer were treated with externally administered hyperthermia and radiation therapy. Thirty-eight fields were treated for microscopic residual disease following excisional biopsy of nodular recurrences and 224 fields were treated electively for areas at high risk for local recurrences adjacent to fields with macroscopic residual disease. Mechanically mapped temperatures were monitored throughout the field in all treatments. All patients had at least one follow-up evaluation at three weeks or more following completion of treatment. The majority of the fields were in patients who had had extensive prior therapy including radiation therapy (54%), chemotherapy (71%), and hormonal therapy (51%). All fields received hyperthermia (1–6 treatments: average 1.74) and radiation therapy (average dose: 42.4 Gy); concurrent hormonal therapy was administered in 37010 of the treatments and no fields received concurrent chemotherapy. The treatments were well tolerated, no life-threatening complications were noted. Averages for all fields of the minimum, maximum, and average measured interstitial temperatures were 40.2°C, 45.3°C, and 42.8°C, respectively. The three-year actuarial local-control rate for all 262 treated fields was 68010. Parameters characterizing the initial breast cancer, the patient and tumor at the time of hyperthermia, and the treatment were studied in univariate and multivariate analysis for correlation with duration of local control within the hyperthermia treatment field. Parameters in the best five covariate model correlating with the duration of local control included: estrogen receptor status of the initial breast cancer, initial T-stage; time from initial breast cancer to first failure; age at hyperthermia; and concurrent radiation dose ( p -value for model
Dielectric and thermophysical properties of different beef meat blends over a temperature range of -18 to +10°C.

Dielectric and thermophysical properties of three different beef meat blends (lean, fat and 50:50 mixture) were evaluated over a range of temperatures from -18 to +10°C. In the region of thawing (-3 to -1°C), dielectric constant (e') and dielectric loss factor (e') values for radio frequency (RF) and microwave (MW) were significantly higher (P<0.05) than at other measured temperatures for the three blends. In the same region, thermal conductivity (k), specific heat (c) and thermal diffusivity (α) also showed significant changes (P<0.05). k and α values were significantly lower, while c values were significantly higher in this region than at other measured temperatures for the three blends. RF (27.12MHz) vs. MW (896 and 2450MHz) frequencies had an important effect (P<0.05) on the measured dielectric properties of the beef meat blends, with a general tendency towards higher values at the RF frequency. Finally, composition significantly influenced (P<0.05) the measured dielectric and thermophysical properties at all temperatures used. These data are of potential value to food technologists in the context of rapid defrosting of meat products.
Developmental regulation of V(D)J recombination and lymphocyte differentiation.

Abstract Recent insights into the mechanism of V(D)J recombination have clarified the direct role of the products of the recombination-activating genes Rag-1 and Rag-2 in site-specific DNA cleavage at recombination signal sequences and have identified components of the general DNA double-strand break repair pathway that participate in the rejoining of the Rag-1 and Rag-2-cut receptor gene segments. The V(D)J reaction is restricted to particular antigen receptor loci in a lineage-specific and stage-specific manner. This specificity appears to involve cis-regulatory elements, some of which also regulate transcription of the germline antigen receptor loci. Early developmental steps in the T and B lineages — including phenotypic differentiation, expansion of precursors, and selection processes — are effected in a stepwise fashion by signals generated, at least in part, by the products of the functionally rearranged antigen receptor genes themselves.
A new double-stranded RNA-binding protein that interacts with PKR

We have identified a 74 kDa double-stranded (ds)RNA-binding protein that shares extensive homology with the mouse spermatid perinuclear RNA-binding (Spnr) protein. p74 contains two dsRNA-binding motifs (dsRBMs) that are essential for preferential binding to dsRNA. Previously, dsRNA-binding proteins were shown to undergo homo- and heterodimerization, raising the possibility that regulation of activity could be controlled by interactions between different family members. Homodimerization is required to activate the dsRNA-dependent protein kinase PKR, whereas hetero-dimerization between PKR and other dsRNA-binding proteins can inhibit kinase activity. We have found that p74 also interacts with PKR, both the wild-type enzyme and a catalytically defective mutant (K296R). While co-expression of p74 and wild-type PKR in the yeast Saccharomyces cerevisiae did not alter PKR activity, co-expression of p74 and the catalytically defective K296R mutant surprisingly resulted in abnormal morphology and cell death in transformants that maintained a high level of p74 expression. These transformants could be rescued by overexpression of the alpha-subunit of wild-type eukaryotic translation initiation factor 2 (eIF2alpha), one of the known substrates for PKR. We hypothesize that competing heterodimers between p74-K296R PKR and eIF2alpha-K296R PKR may control cell growth such that stabilization of the p74-K296R PKR heterodimer induces abnormal morphology and cell death.
Sinter-Forging of Nanocrystalline Zirconia: II, Simulation

A quantitative computer simulation of densification, pore-size evolution, and grain growth during sinter-forging has been developed and applied to the sinter-forging of nanocrystalline yttria (30 mol%)-stabilized zirconia (3Y-TZP) at 1050° and 1100°C. Densification is simulated as a superposition of stress-assisted and plastic-strain-controlled pore-shrinkage mechanisms. Grain growth is simulated as a pore-controlled process during intermediate-stage densification and as a combination of normal (static) grain growth and dynamic grain growth during final-stage densification. The densification portion of the model offers very good agreement with the experiment under a wide variety of imposed forging conditions, despite the absence of adjustable variables. Grain-growth predictions qualitatively illustrate a key feature in the sinter-forging of 3Y-TZP: i.e., the minimization of grain size, as a function of density, under forging conditions that promote high strain rates. This particular effect seems to be due to the quick elimination of large pores by plastic strain while small pores (which shrink by diffusion) are still available to control grain growth.
Assessing some dynamic properties of the living nervous system.

Article de synthese a propos des changements dynamiques des contacts synaptiques, des relations entre les synapses et les cellules gliales et de la configuration des dendrites au niveau des ganglions sympathiques ou parasympathiques, et au niveau de la cornee et du bulbe olfactif de la souris examines a l'aide de la technique d'imagerie in vivo
The formation and role of a phase with glassy appearance in the Tl-Ca-Ba-Cu system

A phase with a glassy appearance has been detected in samples of the Tl–Ca–Ba–Cu system. The presence of such a phase is expected to have a negative effect on the critical current density in a bulk superconductor. Samples of 2-2–2-3 starting composition were prepared from Tl 2 O 3 , BaO 2 , and relatively large particles of CaO and CuO. These samples were then heat-treated at 867°C for various periods of time. The use of large particles of CaO and CuO facilitates the examination of the morphological changes associated with the formation of the superconducting phases. Using scanning electron microscopy, a layer of the 2122 phase was found to form on the surface of the large CaO particles whereas near the surface of the large CuO particles, large voids were observed. By varying some of the experimental conditions, a liquid phase with a composition close to 2-0–2-3 was inferred to form. The voids observed in the surroundings of the CuO particles may be due to the formation of such a melt. This liquid phase, after cooling, apparently leads to the “glassy” phase detected in the reacted samples. This glassy phase may play a role as an intermediate in the formation of the 2122 phase, which could result by a direct reaction between the liquid phase and CaO, A part may remain, however, among the superconducting grains, thus having a negative effect on the critical current density.
Dietary Intake, Body Composition, and Bone Mineral Density in Premenstrual Gymnasts

Abstract LEARNING OUTCOME: To identify the relationships among dietary intake, body composition, and bone mineral density in premenstrual female gymnasts and nongymnasts. Participation in competitive gymnastics has been associated with poor dietary intakes and a history of menstrual cycle interruptions in older female gymnasts. The purpose of this study was to examine the relationships among dietary intakes, body composition, and bone mineral density (BMD) in premenstrual female gymnasts (GYM; n=12; age=10.1 ± 1.2 yrs) and their age- (± 0.02 yrs), height- (± 2.2 cm), and weight- (± 0.03 kg) matched nongymnast controls (CON; n=12; age=10.1 ± 1.0 yrs). Three-day diet records were used to estimate mean daily dietary kilocalorie (kcal), macronutrient, and calcium intakes. Dual energy X-ray absorptiometry (Hologic QDR-1000W, version 5.55) was used to assess body composition and femoral neck, trochanter, Ward's triangle, lumbar spine, and whole body BMD. Mean BMD of GYM were significantly higher than CON at all sites (p These data suggest that participation in gymnastic exercise has an important impact on BMD in premenstrual females consuming adequate levels of dietary calcium, has no adverse effect on kcal and macronutrient consumption, and is associated with FFST and %BF differences at an early age. (Funded, in part, by the SCAN Practice Group, 1996.)
Laboratory and theoretical constraints on the generation and composition of natural gas

Hydrous pyrolysis experiments were conducted at 125 to 375°C and 350 bars to constrain factors that regulate the generation and relative abundance of hydrocarbon and nonhydrocarbon gases during thermal maturation of Monterey, Eutaw, and Smackover shale. Thermogenic gas was generated at temperatures as low as 125°C and increased in abundance with increasing temperature. The relative abundance of individual hydrocarbons varied substantially in response to increasing time and temperature reflecting the chemical processes responsible for their formation. The hydrocarbon fraction of low maturity gas produced via primary cracking of kerogen was composed predominantly of methane. With increasing thermal maturity, the onset of bitumen generation produced longer-chain hydrocarbons causing a decrease in the relative abundance of methane. At high levels of thermal maturity, the absolute and relative abundance of methane increased due to decomposition of bitumen. In all experiments at all temperatures, carbon dioxide was the most abundant volatile organic alteration product. Carbon dioxide was produced directly from kerogen at low thermal maturity and via the decomposition of bitumen and/or kerogen at high thermal maturity. During early stage alteration, kerogen likely represents the dominant source of oxygen in carbon dioxide while at high thermal maturities water may represent an abundant and reactive oxygen source. Hydrogen released during the disproportionation of water is likely consumed during hydrocarbon generation. Theoretical reaction path modeling suggests that the precipitation of calcite may effectively remove carbon dioxide from natural gas if a source of Ca is available within the rock. Thus, carbon dioxide-rich natural gas may be relatively pristine while methane-rich natural gas may reflect the occurrence of secondary reactions involving inorganic sedimentary components. Kinetic analysis of the experimental data indicates a narrow range of activation energies for the generation of C1-C4 hydrocarbons from the Monterey, Smackover, and Eutaw shales. Carbon dioxide generation from the Monterey and Eutaw shales is accounted for by a substantially broader range of activation energies. Application of these data to predict gas formation at temperatures and time scales typical of subsiding sedimentary basins suggests that C1-C4 generation is restricted to relatively high temperatures while carbon dioxide generation occurs at both low and high thermal maturities. Thus, in contrast to the bulk of C1-C4 generation which is predicted to occur after peak bitumen generation, production of carbon dioxide will occur before, during, and after the generation of liquid hydrocarbons.
CIA's queries about Boretsky's criticism of its estimates of Soviet economic growth

Abstract The CIA's attempts to rebut Boretsky's criticism of its estimates of Soviet economic growth have no merit. The improvement of economic intelligence on the USSR will require the intelligence community's return to values-oriented academic-like research and analysis and its abandonment of the CIA's method of physical counts and measures.
Attempt to Detect the Antineutrinos from a Nuclear Reactor by the Cl 37 ( ν ¯ , e − ) A 37 Reaction

Tanks containing 200 and 3900 liters of carbon tetrachloride were irradiated outside of the shield of the Brookhaven reactor in an attempt to induce the reaction ${\mathrm{Cl}}^{37}(\overline{\ensuremath{\nu}}, {e}^{\ensuremath{-}}){\mathrm{A}}^{37}$ with fission product antineutrinos. The experiments serve to place an upper limit on the antineutrino capture cross section for the reaction of 2\ifmmode\times\else\texttimes\fi{}${10}^{\ensuremath{-}42}$ ${\mathrm{cm}}^{2}$ per atom. Cosmic-ray-induced ${\mathrm{A}}^{37}$ was observed and the production rate measured at 14 100 feet altitude and sea level. Measurements with the 3900-liter container shielded from cosmic rays with 19 feet of earth permit placing an upper limit on the neutrino flux from the sun.
Is Travel Distance a Barrier to Veterans' Use of VA Hospitals for Medical-Surgical Care

Lengthy travel distances may explain why relatively few veterans in the United States use VA hospitals for inpatient medical/surgical care. We used two approaches to distinguish the effect of distance on VA use from other factors such as access to alternatives and veterans' characteristics. The first approach describes how disparities in travel distance to the VA are related to other characteristics of geographic areas. The second approach involved a multivariate analysis of VA use in postal zip code areas (ZCAs). We used several sources of data to estimate the number of veterans who had priority access to the VA so that use rates could be estimated. Access to hospitals was characterized by estimated travel distance to inpatient providers that typically serve each ZCA. The results demonstrate that travel distance to the VA is variable, with veterans in rural areas traveling much farther for VA care than veterans in areas of high population density. However, Medicare recipients also travel farther in areas of low population density. In some areas veterans must travel lengthy distances for VA care because VA hospitals which were built over the past few decades are not located close to areas in which veterans reside in the 1990s. The disparities in travel distance suggest inequitable access to the VA. Use of the VA decreases with increases in travel distance only up to about 15 miles, after which use is relatively insensitive to further increases in distance. The multivariate analyses indicate that those over 65 are less sensitive to distance than younger veterans, even though those over 65 are Medicare eligible and therefore have inexpensive access to alternatives. The results suggest that proximity to a VA hospital is only one of many factors determining VA use. Further research is indicated to develop an appropriate response to the needs of the small but apparently dedicated group of VA users who are traveling very long distances to obtain VA care.
Cognitive and motor impairments associated with SIV infection in rhesus monkeys

Cognitive and motor deficits are now recognized as significant clinical features of infection with the human immunodeficiency virus (HIV). Juvenile rhesus macaques infected with simian immunodeficiency virus (SIV) were found to exhibit cognitive and motor deficits characteristic of HIV infection. Impairment on a motor skill task was the most reliable indicator of infection. Various cognitive impairments were also evident. These deficits were related to SIV infection of the brain but not to inflammatory lesions at a particular locus. The results suggest that the SIV-infected rhesus macaque is a valuable model for understanding the cause of HIV-associated central nervous system dysfunction and for developing a treatment.
Sequence complexities of mRNA populations during adult wing development in the silkmoth Antheraea polyphemus

Abstract The total poly A + messenger RNAs of epidermal cells in the wing sac of the silkmoth Antheraea polyphemus as a function of development (which is under the influence of the moulting hormone, 20-hydroxyecdysone) has been analyzed by cDNA-mRNA hybridizations. Kinetic and numerical analysis of homologous hybridizations indicate the messenger populations to be made up of several kinetic classes, the total complexity being similar at all stages of development. Heterologous hybridizations indicate clear differences between two stages: (i) at the beginning of development characterized by growth and development and (ii) at the end of development characterized by differentiation and cuticular secretion. The principal difference between the two stages has been shown, by isolation and characterization of null cDNA (cDNA enriched for the second stage) to be due to the appearance of several hundred new mRNAs belonging to the moderately abundant class at the second stage. Analysis of translation products by SDS-PAGE and immunoprecipitation confirm and extend these results.
More Than Punch and Cookies: A New Look at Parent Orientation Programs

This chapter presents novel approaches to parent orientation programs that are based on emerging family constellations and the changing expectations of parents.
Single-molecule tracking of small GTPase Rac1 uncovers spatial regulation of membrane translocation and mechanism for polarized signaling

Polarized Rac1 signaling is a hallmark of many cellular functions, including cell adhesion, motility, and cell division. The two steps of Rac1 activation are its translocation to the plasma membrane and the exchange of nucleotide from GDP to GTP. It is, however, unclear whether these two processes are regulated independent of each other and what their respective roles are in polarization of Rac1 signaling. We designed a single-particle tracking (SPT) method to quantitatively analyze the kinetics of Rac1 membrane translocation in living cells. We found that the rate of Rac1 translocation was significantly elevated in protrusions during cell spreading on collagen. Furthermore, combining FRET sensor imaging with SPT measurements in the same cell, the recruitment of Rac1 was found to be polarized to an extent similar to that of the nucleotide exchange process. Statistical analysis of single-molecule trajectories and optogenetic manipulation of membrane lipids revealed that Rac1 membrane translocation precedes nucleotide exchange, and is governed primarily by interactions with phospholipids, particularly PI(3,4,5)P3, instead of protein factors. Overall, the study highlights the significance of membrane translocation in spatial Rac1 signaling, which is in addition to the traditional view focusing primarily on GEF distribution and exchange reaction.
Prognosis of occupational asthma

Background Occupational asthma (OA), is an important clinical condition with substantial morbidity and associated costs. Since the original description of OA we have learned a great deal about the natural history. The prognosis of OA is determined by many factors. These factors and confounding variables in the presentation of OA will be presented. Results A review of the available literature indicates that OA may have complete resolution or may persist for years following its initial presentation. Conclusion The importance of timely removal or adequate respiratory protection from potential sources of OA is highlighted.
Cyberterrorism: The Sum of All Fears?

Cyberterrorism conjures up images of vicious terrorists unleashing catastrophic attacks against computer networks, wreaking havoc, and paralyzing nations. This is a frightening scenario, but how likely is it to occur? Could terrorists cripple critical military, financial, and service computer systems? This article charts the rise of cyberangst and examines the evidence cited by those who predict imminent catastrophe. Psychological, political, and economic forces have combined to promote the fear of cyberterrorism. From a psychological perspective, two of the greatest fears of modern time are combined in the term “cyberterrorism.” The fear of random, violent victimization segues well with the distrust and outright fear of computer technology. Many of these fears, the report contends, are exaggerated: not a single case of cyberterrorism has yet been recorded, hackers are regularly mistaken for terrorists, and cyberdefenses are more robust than is commonly supposed. Even so, the potential threat is undeniabl...
A blowup result for the critical exponent in cones

We consider positive solutions of the initial value problem foru t=Δu+u p in conesD=R +×Ω⊆R N (Ω⊆S N−1). In an earlier paper, we determined a critical exponentp *(Ω) with the following properties: (a) if 1<p<p *, then all nontrivial solutions blow up in finite time (blowup case); (b) ifp>p *, then there are nontrivial global solutions (global existence case). Here we show thatp * belongs to the blowup case. This generalizes a well-known result for the critical exponentp *=1+2/N inD=R N .
A single neuron analysis of buccal cavity representation in the sensory trigeminal complex of the cat

Abstract The receptive fields and modality of stimulus necessary to elicit discharges in neurons of the sensory trigeminal nuclear complex were studied in the decerebrate cat. The buccal cavity representation was found to be in the medial portion of the sensory V complex with the mandibular division represented dorsal to the maxillary. Each portion of the periphery appears to be represented by a rostro-caudal line of cells extending from the principal sensory V nucleus to the caudal portion of the descending root. The relation of the morphology of the trigeminal sensory complex to the characteristics of regional and modality representation is presented. The discharge properties of neurons excited from buccal structures, especially teeth, are characterized for light touch, pressure and cruder physiological stimuli. A reinterpretation of the nature of pain representation is discussed.
Hypoesthesia in the distal residual limb of amputees.

Objective To test the emerging hypothesis that there is polymodal fiber degeneration/loss in distal residual limbs (DRL) of amputees. Design Prospective qualitative and quantitative psychophysical testing. Setting A pain research center at an urban academic rehabilitation hospital. Participants Forty-four amputees (32 with pain, 12 without pain) with a single (upper or lower) limb amputation. Subjects are a clinical "convenience" sample derived from our amputee or prosthetic clinics. Methods Interventions were prospectively acquired psychophysical tests. The primary quantitative test was thermal Quantitative Sensory Testing (tQST) using a Peltier type thermal testing device, assessing sites on the DRL compared with anatomically similar regions on the contralateral "unaffected" extremity. Results Perceptual responses for several qualitative psychophysical stimuli and perceptual thresholds for tQST cold sensation were significantly reduced in the DRL (t(43) = −2.613, P = .012). There were no significant tQST differences in thresholds for warm perception, cold pain, or hot pain ( P > .05). Conclusion These results show a point prevalence of differential hypoesthesia in distal residual limbs. There was a selective loss of cold, but not warm perception or threshold for hot or cold pain by tQST. There are several possible explanations for this polymodal and selective hypoesthesia; specifically, these data may be indicative of a differential "dying back" peripheral neuropathy of the DRL, which may be operational in such clinical features as postamputation pain.
Alternatives in Paleocene exploration West of Shetland: a case study

Synopsis This paper illustrates oil exploration in the West of Shetlands area from 1995 to 2001 by documenting the history of Block 205/9, awarded in the UK 16th Licensing Round in 1995. Good quality Paleocene sands had been encountered in the 1989 well 205/9-1 in the down-dip part of the block, and equivalent sands were absent on the adjacent Flett Ridge to the SE, setting up the possibility of a pinchout play. The first well testing the play, 205/8-1, was drilled on the overall pinchout on 2D seismic data, but 3D seismic data were acquired across the area to better delineate the depositional systems. The first well drilled on the 3D data to test the sand pinchout, 205/14-3, failed to encounter sands in communication with those in 205/9-1, so attention turned to alternative stratigraphic traps highlighted by seismic amplitude anomalies. Detailed evaluation of the seismic data revealed that the attractive seismic amplitude response of one potential prospect was actually an artefact associated with overlying basalt. Further analysis of the 3D seismic attributes identified a tongue of sand south of 205/9-1, and analysis of magnetic fabrics from core data in 205/9-1 revealed that sand was input to this area from the NE, contrary to previous models. Unfortunately the seismic attributes, supported by fluid inclusion data, suggested that the sand was water-wet. As a result of the evaluation work, the block was relinquished in 1999 without further drilling. While there is undoubtedly scope for stratigraphic traps in the area to prove hydrocarbon-bearing, experience on the 205/9 block and other studies led to a refocusing on dip-closed structures, and a resulting discovery, the first in the Faroes, consisted of 170 m of hydrocarbon-bearing sands in the T10 Paleocene interval.
Recent and remote memory dissociation: Medication effects and hippocampal function in schizophrenia

Neuropsychological measures of recent and remote memory as well as general attention were administered to two groups of DSM-III-R schizophrenic patients in a within-subject repeated measures design across a 3-week interval. One group of patients ( n = 12) was maintained on haloperidol for both test sessions, whereas a second group ( n = 9) was tested first on haloperidol and again 3-weeks drug free. Patients received no adjunctive anticholinergic medication during the study. No differences were observed between the patient groups in level of psychotic symptomatology or general attention across the two test sessions. Patients withdrawn from haloperidol showed significant decreases in recent verbal memory function, while at the same time demonstrating significant increases in remote verbal memory. We speculate that the observed pattern of results is consistent with medial temporal lobe dysfunction particularly prominent in the left hemisphere as patients become drug free, and provides support for the existence of state-dependent cognitive changes in schizophrenia.
Retinoid cycling proteins redistribute in light-/dark-adapted octopus retinas.

In cephalopods, the comblex rhodopsin-retinochrome system serves to regenerate metarhodopsin and metaretinochrome after illumination. In the dark, a solubleprotein, retinal-binding protein (RALBP), shuttles 11-cis retinal released from metaretinochrome located in the photoreceptor inner segments to metarhodopsin present in the rhabdoms. While in the rhabdoms, RALBP delivers 11-cis retinal to regenerate rhodopsin and in turn binds the all-trans isomer released by metarhodopsin. RALBP then returns all-trans retinal to the inner segments to restore retinochrome. The conventional interpretation of retinoid cycling is contradicted by immunocytochemical studies showing that, in addition to rhodopsin, retinochrome is present in the rhabdomal compartment, making possible the direct exchange of chromophores between the metapigments with the potential exclusion of RALBP. By using immunofluorescence and laser scanning confocal microscopy, we have precisely located opsin, aporetinochrome, and RALBP in light-/dark-adpated octopus retinas. We found differences in the distribution of all three proteins throughout the retina. Most significantly, comparison of cross sections though light- and dark-adpated rhabdoms showed a dramatic shift in position of the proteins. In the dark, opsin and retinochrome colocalized at the base of the rhabdomal microvilli. In the light, opsin redistributed along the length of the microvillar membranes, and retinochrome retreated to a location that is perhaps extracellular. RALBP was present in the core cytoplasm of the photoreceptor outer segments in the dark, and RALBP moved to the periphery in the light. Because of the colocalization of opsin and retinochrome in the dark, we believe that the two metapigments participate directly in chromophore exchange. RALBP may serve to transport additional chromophore from the inner segments to the rhabdoms and may not be immediately involved in the exchange process. © 1995 Wiley-Liss, Inc.
Acute management of extreme neonatal jaundice : the potential benefits of intensified phototherapy and interruption of enterohepatic bilirubin circulation

Increasing numbers of neonates are being admitted to hospital because of extreme jaundice. Phototherapy should be very effective in such infants, because the efficacy of phototherapy is proportional to the concentration of bilirubin in the skin. Here, I report on four infants who were admitted for indirect serum bilirubin levels of >500 micromol/l (>>30 mg/dl). In one of them, unrecognized Rhesus immunization was the main cause of hyperbilirubinemia, while in the other three increased enterohepatic circulation of bilirubin was thought to be an important contributory factor. In all four infants phototherapy (11-14 microW/cm2/nm) with whole body exposure plus ad lib feeding with milk were initiated immediately upon admission to the nursery. After 2h serum bilirubin values were reduced by 170-185 micromol/l (10-11 mg/dl) in the first three infants, while in the fourth infant a reduction of 195 micromol/l (11.3 mg/dl) was seen in the 5 h interval between the first and second bilirubin measurement. This experience suggests that in some infants with extreme jaundice, intensified phototherapy plus feeding with milk may be very effective in reducing serum bilirubin levels. Even if an exchange transfusion is performed, using this strategy in the waiting period may be beneficial, as both the rapid reduction in serum bilirubin levels as well as the conversion of significant amounts of bilirubin into water-soluble isomers may reduce the risk of neurotoxicity.
CLINICIAN IDENTIFIED BARRIERS TO CLINICAL RESEARCH

Involvement of front-line clinicians in clinical studies is crucial for quality marriage and family therapy effectiveness research. To identify common barriers to clinical research, 326 clinical members of the American Association for Marital and Family Therapy from three geographically diverse states were asked to describe their willingness to participate in a hypothetical research project. Therapists cited time constraints, outside limitations, client concerns, and a lack of understanding about and involvement in the study as major reasons for refusal to participate. Recommendations for building collaborative relationships between clinicians and researchers as well as future research are addressed.
Slow repair of lipid peroxidation-induced DNA damage at p53 mutation hotspots in human cells caused by low turnover of a DNA glycosylase

Repair of oxidative stress- and inflammation-induced DNA lesions by the base excision repair (BER) pathway prevents mutation, a form of genomic instability which is often observed in cancer as 'mutation hotspots'. This suggests that some sequences have inherent mutability, possibly due to sequence-related differences in repair. This study has explored intrinsic mutability as a consequence of sequence-specific repair of lipid peroxidation-induced DNA adduct, 1, N(6)-ethenoadenine (eA). For the first time, we observed significant delay in repair of ϵA at mutation hotspots in the tumor suppressor gene p53 compared to non-hotspots in live human hepatocytes and endothelial cells using an in-cell real time PCR-based method. In-cell and in vitro mechanism studies revealed that this delay in repair was due to inefficient turnover of N-methylpurine-DNA glycosylase (MPG), which initiates BER of eA. We determined that the product dissociation rate of MPG at the hotspot codons was ≈5-12-fold lower than the non-hotspots, suggesting a previously unknown mechanism for slower repair at mutation hotspots and implicating sequence-related variability of DNA repair efficiency to be responsible for mutation hotspot signatures.
Milk lipid digestion in the neonatal dog: the combined actions of gastric and bile salt stimulated lipases.

Abstract Intragastric lipolysis may be particularly important for the digestion of milk lipid since milk fat globules are resistant to pancreatic lipase without prior disruption; milk bile salt stimulated lipase (BSSL) may supplement further intestinal hydrolysis. Previous information on gastric lipolysis has been based primarily on in vitro studies using artificial lipid emulsions containing a single component fatty acid and have focused on the preferential release of medium-chain fatty acids. The actual contribution of these enzymes to overall fat digestion in vivo on natural substrates has rarely been studied, however. The neonatal dog is an excellent model in the study of lipid digestion because, like the human, milk lipids are high in long-chain unsaturated fatty acids, milk contains BSSL and gastric lipase is the predominant lipolytic enzyme acting in the stomach. We used a combination of in vivo studies with in vitro incubations to investigate digestion of milk lipid by gastric and milk (BSSL) lipases in the suckling dog. In the first 4 weeks postpartum, 14–41% and 42–60% of milk triacylglycerol was hydrolyzed to primarily diacylglycerol and free fatty acid (FFA) in the first 30 and 60 min in the stomach, respectively. Milk lipid contained high levels (63%) of long-chain unsaturated fatty acids, which were preferentially released as FFA during in vivo gastric lipolysis, consistent with the actions and stereospecificity of gastric lipase. While levels of hydrolysis in gastric aspirates were significantly different (by age and time in stomach) at the start of in vitro studies, total hydrolysis in all incubation systems plateaued at about 65%, suggesting product inhibition by the long-chain FFA, but to a much lesser degree than previously expected from in vitro studied. The magnitude of in vivo intragastric lipolysis was 3- to 6-times greater than that predicted by in vitro assays using either milk lipid or labeled emulsion as substrate, respectively. Prior exposure to intragastric lipolysis resulted in 30% hydrolysis by BSSL compared to 5% hydrolysis without prior exposure. We suggest that previous in vitro studies have largely underestimated the actual degree of intragastric lipolysis that can occur and its activity on long-chain fatty acids; this study indicates the importance of the combined mechanism of gastric lipase and BSSL to fat digestion in the suckling neonate.