cssi/SciSciGPT-SciSciNet huggingface dataset:
Flt-1-mediated Down-regulation of Endothelial Cell Proliferation through Pertussis Toxin-sensitive G Proteins, βγ Subunits, Small GTPase CDC42, and Partly by Rac-1 *

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) promotes its function primarily by activating two receptor tyrosine kinases, Flt-1 (VEGFR-1) and KDR (VEGFR-2). Recently, it has been shown that KDR is responsible for VPF/VEGF-stimulated endothelial cell (EC) proliferation and migration, whereas Flt-1 activation down-modulates KDR-mediated EC proliferation. Although KDR-mediated EC proliferation and migration have been extensively studied, much less is known about Flt-1-mediated antiproliferation. Here, we demonstrate that Flt-1-mediated antiproliferative activity can be blocked completely by the dominant negative mutant of CDC42 (CDC42-17N) and partially by a Rac1 dominant negative mutant (Rac1-17N) but is not affected by a RhoA dominant negative mutant (RhoA-19N). Both CDC42-17N and Rac1-17N increase the intracellular Ca(2+) mobilization in response to VPF/VEGF but have no effect on KDR and MAPK phosphorylation. Using the chimeric-receptor EGLT in which the extracellular domain of epidermal growth factor receptor was fused to the transmembrane and intracellular domains of Flt-1, we also demonstrate that CDC42 and Rac1 are activated by EGLT. Previously, we showed that phosphatidylinositol 3-kinase is required for Flt-1-mediated antiproliferative activity, but phospholipase C is not required. As expected, CDC42 and Rac1 activation mediated by EGLT can be completely inhibited by PI3K inhibitors, wortmannin and LY294002, and the p85 dominant negative mutant but not by either the phospholipase C inhibitor, or an intracellular Ca(2+) chilator BAPTA/AM. Surprisingly, pertussis toxin and overexpression of the free Gbetagamma-specific sequestering minigene hbetaARK1(495) also inhibit EGLT-mediated CDC42 and Rac1 activation completely. Moreover, pertussis toxin treatment also increases the intracellular Ca(2+) mobilization and inhibits the antiproliferation activity, thus suggesting that pertussis toxin-sensitive G proteins and the Gbetagamma subunits are involved in the signaling pathway of Flt-1 that down-regulates EC proliferation. Taken together, these results further expand our understanding of Flt-1-mediated antiproliferative activity in VPF/VEGF-stimulated endothelium.
Progress in the design of selectors for buckminsterfullerene

Abstract The chromatographic retentions of buckminsterfullerene (C60), the related C70 carbon cluster, and several polycyclic aromatic hydrocarbons are evaluated using ten high-performance liquid chromatography stationary phases, including several stationary phases designed specifically for recognition of the fullerenes. All of the stationary phases examined provide some degree of retention and selectivity in the separation of C60 and C70. A novel tripodal π-acidic stationary phase designed for simultaneous multipoint interaction with buckminsterfullerene provides the greatest retention and the greatest separation factor for the C60 C70 mixture.
Gravitational time delay due to a spinning string

We show that gravity around a straight cosmic string that carries angular momentum per unit length J induces a delay between the arrival time of two particles that describe an arbitrary closed trajectory around the string with the same speed at each point but in opposite directions. The time delay is 16..pi..GJ, where G is Newton's constant. The particle delayed is the one that circles the closed path in the sense contrary to the angular momentum. As a consequence, double images of a star produced by the string acting as a gravitational lens will acquire a relative time delay, thus providing a mechanism, at least in principle, to measure the string angular momentum. We argue, however, that in any realistic model the time delay effect is negligible. We also discuss other possible implications of this effect in 2 /plus/ 1 dimensions. 13 refs., 1 fig.
Adolescent mental health: Prevention and intervention by Ogden, T., and Hagen, K. A.

This comprehensive and informative book, written by researchers Terje Ogden, of the Norwegian Center for Child Behavioral Development, and Kristine Amlund Hagan, of the Center for Adolescent Mental...
Outcomes of autologous and allogeneic blood or marrow transplantation for mantle cell lymphoma

Abstract To evaluate high-dose therapy and autologous or allogeneic blood or marrow transplantation (BMT) for mantle cell lymphoma, patients receiving BMT for newly diagnosed or relapsed mantle cell lymphoma were identified through the registry at Johns Hopkins. The pathologic diagnostic criteria were reviewed, and details of the presentation, transplant procedure, and survival outcomes were determined. Fifty-eight patients were identified, of whom 64% underwent transplantation in first remission and 12% had primary induction failure. Nineteen patients (one third) received an allograft. Preparative regimens consisted of cyclophosphamide in combination with either busulfan or total body irradiation. On multiple regression analysis, transplantation after 1 or more relapses (hazard ratio, 2.98; P = .02), primary induction failure (hazard ratio, 5.39; P = .002), and allogeneic transplantation (hazard ratio, 3.03; P = .007) were associated with an inferior event-free survival (EFS). However, EFS curves were not statistically different for autologous and allogeneic BMT performed in first remission, with an estimated 3-year EFS approaching or equaling 70%. Primary induction failure and residual bone marrow involvement were the only statistically significant predictors of relapse on multiple regression analysis. At 3 years, the estimated EFS for the entire cohort after BMT was 51%, the probability of relapse was 31%, and the overall survival was 59%. The benefit of autologous or allogeneic BMT for mantle cell lymphoma is thus most apparent when transplantation is performed in first remission. Whether allogeneic BMT ultimately confers an advantage because of a graft-versus-lymphoma effect remains to be determined.
Effect of cyclic loading and environmental aging on the fracture toughness of dental resin composite

Objective The main purpose of this study was (1) to investigate the effects of cyclic loading and environmental aging on three dental resin composites with different filler compositions: a fiber filler, a hybrid filler, and a microfill; and (2) to predict fracture in dental resin composite under mixed-mode loading conditions. Methods Diametral disk specimens 25 mm in diameter and 2 mm in thickness were used in this study. Two methods were used for generating initial cracks in the specimen. The first method involved machining a 3-mm notch in the center of the disk specimens, and then the notch tips were sharpened with a 0.2-mm-diameter jeweler's saw blade. In the second method for obtaining sharper crack tips, a three-way wedge was forced into a 3.175-mm hole drilled in the center of the specimen, resulting in sharp cracks emanating from the notch tips. Cyclic Tests The specimens were aged for 4 months in air, water, artificial saliva, and a 50/50 (by volume) mixture of ethanol and water at room temperature in sealed polyethylene containers. Both unaged and aged specimens (5 specimens for each variable) were subjected to cyclic loading at a frequency of 5 Hz with sinusoidal loads cycling for 1, 1000, and 100,000 cycles at a load level ∼60% of the fracture load for noncycled specimens. Following load cycling, the specimens were tested in compression in a displacement-controlled loading mode at a loading rate of 1.27 mm/min. Results Test results show that aging in a 50/50 alcohol–water mixture lowered the fracture toughness of dental resin composite, which was further reduced by cyclic loading. Mixed-mode tests The maximum tensile stress (MTS) criterion was used to predict fracture in dental resin composite under mixed-mode loading conditions. The loads at failure were used as input into a finite element model. After obtaining the stress field in the specimens by the finite element method, the mixed-mode stress intensity factors were calculated using an interaction energy integral method. Results Good agreement was obtained between the fracture envelope predicted by the MTS criterion and the experimental fracture toughness data. Hence, it can be concluded that it is only necessary to characterize the mode I fracture toughness to fully characterize the mixed-mode behavior of the dental resin composites that were considered in the present study. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007
ENGINEERING PROPERTIES OF RECYCLED PLASTIC PINS FOR SLOPE STABILIZATION

An ongoing demonstration project has shown the feasibility of using slender (90 mm x 90 mm x 2.4 m) recycled plastic pins (RPPs) for in situ reinforcement of slopes and embankments. The technique uses RPPs driven into the face of the slope in a grid pattern to intercept the sliding surface and pin the slope. The engineering properties of the RPPs, including the compressive, tensile, and flexural strength along with creep behavior, dictate the design and construction practice. Constituent materials and manufacturing processes are highly variable among the more than 30 U.S. manufacturers. A specification for acceptance of the members is needed; however, before an effective specification can be developed, the appropriate engineering properties and design requirements for the RPPs must be determined. The engineering properties and driving performance of four different types of members were evaluated and are reported on. Additional evaluations are under way.
A leucine residue "Gates" solvent but not O2 access to the binding pocket of phascolopsis gouldii hemerythrin.

Abstract A leucine residue, Leu-98, lines the O2-binding pocket in all known hemerythrins. Leu-98 in recombinant Phascolopsis gouldii hemerythrin, was mutated to several other residues of varying sizes (Ala, Val), polarities (Thr, Asp, Asn), and aromaticities (Phe, Tyr, Trp). UV-visible and resonance Raman spectra showed that the di-iron sites in these L98X Hrs are very similar to those in the wild type protein, and several of the L98X hemerythrins formed stable oxy adducts. Despite the apparently tight packing in the pocket, all of the L98X Hrs except for L98W, had second order O2 association rate constants within a factor of 3 of the wild type value. Similarly, the O2 dissociation rate constant was essentially unaffected by substitutions of larger (Phe) or smaller (Val, Thr) residues for Leu-98. L98Y Hr showed a 170-fold decrease in the O2 dissociation rate constant and a large D2O effect on this rate, which are attributed to a hydrogen-bonding interaction between the Tyr-98 hydroxyl and the bound O2. Significant increases in autoxidation rates were observed for all of the L98X Hrs other thanX = Tyr. These increases in autoxidation rates are attributed to increased solvent access to the binding pocket caused by inefficient packing (Phe), smaller size (Val, Ala), or increased polarity (Thr, Asp, Asn) of the residue 98 side chain. A leucine at position 98 appears to have the optimal size, shape, and hydrophobicity for inhibition of solvent access. Thus, “gating” of small molecule access to the binding pocket of Hr by Leu-98 is not evident for O2, but is evident for solvent.
The origins of the ‘contra war’ in Nicaragua: The results of a failed development model

This article considers the causes of the ‘Contra War’ in Nicaragua during the 1980s. This conflict has often been portrayed as an American ‘proxy war’ fought by Somoza's former National Guard against a regime supported by most common Nicaraguans. This article proposes an alternate view. The Managua regime, with the advice and assistance of the Soviet bloc, pursued a model of political consolidation and economic development followed by other Third World Marxist‐Leninist states. As in other ‘states of socialist orientation’ in the 1970s and 1980s, this one encountered considerable popular resistance. The conflict in Nicaragua, thus, was a civil war caused by Sandinista policies.
Two types of cholinergic innervation in cortex, one co-localized with vasoactive intestinal polypeptide

The existence of cholinergic neuronal cell bodies in mammalian cerebral cortex was long the subject of much controversy (see ref. 1 for review). Recently, however, a specific cholinergic marker, the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT, E.C.2.3.1.6), was demonstrated by immunohistochemical methods to be present in bipolar neurones in rat cortex2,3. Here we show that at least 80% of these intrinsic cholinergic neurones also contain immunoreactivity for vasoactive intestinal polypeptide (VIP), a neuroactive peptde found to be present in a subpopulation of cortical neurones4. On the other hand, we find that the ChAT-positive cells in the basal forebrain, which are another major source of cholinergic innervation of the cortex5–8, contain no detectable VIP-immunoreactivity. In addition, we have observed by both light and electron microscopy that some VIP- and some ChAT-positive structures in cortex are closely associated with blood vessels.
THE DEEP SPACE 1 EXTENDED MISSION: CHALLENGES IN PREPARING FOR AN ENCOUNTER WITH COMET BORRELLY

Abstract Following the successful conclusion of its 11-month primary mission in September 1999, Deep Space 1 embarked on an ambitious extended mission. The spacecraft is using its ion propulsion system to help deliver it to an encounter with comet 19P/Borrelly in September 2001. Along the way, the very small operations team has faced numerous challenges with an aging and debilitated spacecraft that was not designed for a comet encounter. The progress in reaching comet Borrelly is described as are the plans for attempting to return science data from this high-risk conclusion to the extended mission.
Primary repair of retracted distal biceps tendon ruptures in extreme flexion

Background Distal biceps tendon ruptures may have tendinous retraction, making primary repair difficult and calling into question the need for graft reconstruction. The decision for when to primarily fix or augment high-flexion repairs has not been addressed. We hypothesized high-flexion repairs would have good outcomes without graft augmentation. The purpose of this study was to examine allograft use and outcomes of distal biceps tendon ruptures requiring repair in greater than 60° of flexion. Methods This was a retrospective case-control study 188 distal biceps tendon repairs; of these, 19 chronic and 4 acute cases were identified with repairs of >60° of flexion using a 2-incision technique. Graft need, complications, and Mayo Elbow Performance Score to assess function, were examined with a record review. Patients were surveyed regarding return to work and subjective satisfaction. A control group matched for surgeon, chronicity, and age, but without a high-flexion repair, was compared with cases by using the Student paired t test. Results Graft augmentation was used in 1 patient with poor tendon quality. The Mayo Elbow Performance Score was 100 for all 23 patients, with extension/flexion range of motion from 3° to 138°. All were subjectively "very satisfied/satisfied," with full work return, yet 3 reported mild fatigability. There were 4 complications: 3 transient lateral antebrachial cutaneous neurapraxias and 1 rerupture at the myotendinous junction after retrauma. Differences between cases and controls were not statistically significant. Conclusion Contracted distal biceps tendons may be reliably reattached to their anatomic insertion with up to 90° of elbow flexion. This lessens the need for reconstruction in such circumstances.
Established Medical Therapy for Benign Prostatic Hyperplasia

Benign prostatic hyperplasia is characterized by smooth muscle and epithelial proliferation primarily within the prostatic transition zone that can cause a variety of problems for a patient, the most frequent being bothersome lower urinary tract symptoms. In most cases, medical therapy has become the first-line treatment modality of choice, with a variety of pharmacologic mechanisms proving to be beneficial. Several large trials have shown the efficacy of alpha-receptor blocking and 5-alpha reductase inhibiting medications when used alone and in combination. Newer data has shown the benefit of anti-muscarinic medications in specific populations who suffer from bladder outlet obstruction causing storage urinary symptoms. Phytotherapeutic supplements are numerous and used frequently; however, data supporting safety and efficacy is limited, making treatment recommendations difficult. The available clinical trial data for all of these types of therapy is discussed in this article.
Measured wideband HF mid-latitude channel characteristics

The authors present the results of HF ionospheric channel measurements on a 2000-km midlatitude path between Florida and Massachusetts performed during September 1988 and February/March 1989 using a 1-MHz bandwidth direct-sequence-pseudonoise (DSPN) probing signal. The channel impulse response is extracted by correlating the received probe signal with a local DSPN reference. Doppler information is obtained by Fourier-transforming a succession of these impulse responses. The channel is characterized in terms of its time, its Doppler spread, and the autocorrelation and distribution functions of the received power. The data indicate that this particular channel can operate within 2 dB of the ideal matched-filter signal-to-noise ratio given (1) a decision-directed Rake modem without Doppler correction and (2) a low-overhead backlink for infrequent (a few times, a minute at most) and small (1- or 2-dB increments) transmit power adjustments. >
Cytogenetic heterogeneity in blast crisis (BC) of chronic myelogenous leukemia (CML).

New cytogenetic findings are reported in a patient who entered into an accelerated blastic phase of chronic myelogenous leukemia (CML). The cytogenetic findings of this case can be described as 46, xy, t (5; 7) (q31; q11), t (9; 22) (q34; q11), Ph'. The prognostic implications in such patients with rare and unusual cytogenetic findings are discussed.
Copper toxicity across salinities from freshwater to seawater in the euryhaline fish Fundulus heteroclitus: Is copper an ionoregulatory toxicant in high salinities?

Two waterborne Cu exposures were performed to investigate if Cu is an ionoregulatory toxicant at all salinities in the killifish, Fundulus heteroclitus. A 30-day flow through exposure in 0 (FW), 5, 11, 22, and 28 ppt (SW) and three [Cu]’s (nominal 0, 30, and 150 gC u L −1 ) revealed no apparent Cu induced mortality at the intermediate salinities and high mortality in FW and SW. Fish were sampled at 4, 12, and 30 days after the start of the exposure and both Na + /K + adenosine triphosphatase (Na + /K + ATPase) and carbonic anhydrase (CA) activity in the gill and intestine as well as whole body [Na + ], and [Cl − ] were measured. At the high [Cu] a reduction of whole body [Na + ] after 4 days of exposure in FW was the only physiological parameter influenced. A second static 24 h Cu exposure was performed in FW, 5, 13, and 29 ppt (SW) and two [Cu]’s (nominal 0 and 110 gC u L −1 ). In addition to the parameters listed above, ammonia flux was measured at all salinities and Na + flux was measured in FW fish. Cu affected ionoregulation in FW where decreased Na + uptake associated with inhibition of Na + /K + ATPase led to decreased whole body [Na + ] after 24 h. The only affected parameter in SW was net ammonia excretion suggesting that Cu is not an ionoregulatory toxicant in SW at the concentrations employed. We propose that physiology rather than chemistry explain much of the variation in Cu toxicity seen across salinities.
Development of a heavy-duty chassis dynamometer driving route:

AbstractThere is presently a lack of realistic driving cycles or schedules for the chassis dynamometer emissions testing of heavy-duty trucks. This research effort was motivated by the need for representative emissions measurement techniques to compare alternatively fuelled trucks with their diesel or gasoline counterparts operating in heavy-duty truck applications. Speed versus time and video recording data gathered from trucks in local delivery use were used to develop a city/suburban heavy vehicle route (referred to as the CSHVR) for Class 7 (11 794-14969 kg gross vehicle weight) and Class 8 (14969-36287 kg) delivery trucks. Statistical data were gathered on actual truck driving behaviour, as well as 60 h of actual speed versus time driving information. A cycle was then developed by joining microtrips from the actual truck operation and verifying that it was representative of the whole database. A driving route was derived from this cycle with the help of the video data, and with the vehicle decelerati...
Mucosal Vaccination with a Multivalent, Live-Attenuated Vaccine Induces Multifactorial Immunity against Pseudomonas aeruginosa Acute Lung Infection

Many animal studies investigating adaptive immune effectors important for protection against Pseudomonas aeruginosa have implicated opsonic antibody to the antigenically variable lipopolysaccharide (LPS) O antigens as a primary effector. However, active and passive vaccination of humans against these antigens has not shown clinical efficacy. We hypothesized that optimal immunity would require inducing multiple immune effectors targeting multiple bacterial antigens. Therefore, we evaluated a multivalent live-attenuated mucosal vaccination strategy in a murine model of acute P. aeruginosa pneumonia to assess the contributions to protective efficacy of various bacterial antigens and host immune effectors. Vaccines combining 3 or 4 attenuated strains having different LPS serogroups were associated with the highest protective efficacy compared to vaccines with fewer components. Levels of opsonophagocytic antibodies, which were directed not only to the LPS O antigens but also to the LPS core and surface proteins, correlated with protective immunity. The multivalent live-attenuated vaccines overcame prior problems involving immunologic interference in the development of O-antigen-specific antibody responses when closely related O antigens were combined in multivalent vaccines. Antibodies to the LPS core were associated with in vitro killing and in vivo protection against strains with O antigens not expressed by the vaccine strains, whereas antibodies to the LPS core and surface proteins augmented the contribution of O-antigen-specific antibodies elicited by vaccine strains containing a homologous O antigen. Local CD4 T cells in the lung also contributed to vaccine-based protection when opsonophagocytic antibodies to the challenge strain were absent. Thus, multivalent live-attenuated vaccines elicit multifactorial protective immunity to P. aeruginosa lung infections.
Eukaryote-dominated biofilms and their significance in acidic environments.

Biodiversity of benthic eukaryotic microorganisms in highly acidic (pH ≤ 3.5) aquatic environments is limited to species that have developed strategies to tolerate elevated concentrations of H+ and dissolved metals and low nutrients levels that commonly characterize these environments. To survive adverse conditions, some algae, protozoa, and fungi have developed mechanisms to make their cell membranes impermeable to protons and maintain cytosolic pH at near neutral levels; others have developed a cell boundary mechanism that blocks H+ ions from entering the cell. High concentrations of heavy metals are also toxic, adversely impacting growth by disrupting physiological, biochemical, or metabolic processes. Some algae, fungi, and protozoans are able to tolerate high metal concentrations via metal complexation outside the cell, extracellular binding and precipitation of metals, reduced metal uptake, increased metal efflux, and detoxification or compartmentalization of metals within the cell. In acidic enviro...
Survival and Growth of Japanese Medaka ( Oryzias latipes ) Exposed to Trichlorethylene at Multiple Life Stages: Implications of Establishing the Maximum Tolerated Dose for Chronic Aquatic Carcinogenicity Bioassays

To evaluate the most sensitive life stage of the Japanese medaka (Oryzias latipes) at which to determine the maximum tolerated dose for chronic carcinogenicity bioassays, the effects of trichloroethylene (TCE) on growth and survival of the medaka were examined at several life stages. A series of 7-day flow-through exposures was conducted with medaka at 4, 7, 10, 13, 16, 28, 42, and approximately 180 days posthatch. Growth, measured as standard length and area, was more sensitive than survival in fish that were 4 to 13 days old at the start of the tests. Medaka 7, 10, and 13 days posthatch established the lowest observed effect concentration for all life stages, based on growth at 8.8 to 10.1 mg/L. There were no significant effects on growth of fish more than 16 days old at the study's initiation. Values of lethal concentration to 50% of the test organism calculated for the various life stages ranged from 23.0 mg/L for 16-day-old fry to 37.0 mg/L for 4-day-old fry. Survival was most affected by TCE in fish...
Staged treatment of invasive carcinoma of bladder

Abstract A three-stage approach to carcinoma of the bladder consists of preliminary urinary diversion, radiation therapy, and simple total cystectomy. We have used this method for more than ten years. The survival rates are the same as generally published, and the morbidity and mortality constrast favorably with other reports. To date, no patient has died within two months of completion of the course of therapy.
Comparison of Postfire Soil Water Repellency Amelioration Strategies on Bluebunch Wheatgrass and Cheatgrass Survival

Soil water repellency can limit postfire reseeding efforts and thus increase the susceptibility of a site to weed invasion. We evaluated the effectiveness of wetting agents and simulated anchor chaining for improving seedling growth and survival in water-repellent soil, for the native perennial bluebunch wheatgrass (Pseudoroegneria spicata) and invasive annual cheatgrass (Bromus tectorum). Research was performed in a glasshouse, on 20-cm-diameter soil cores that were excavated from underneath burned Utah juniper (Juniperus osteosperma) trees. The experiment was arranged as a randomized split-plot design, with the two grass species sown separately under four soil treatments: 1) no treatment (control), 2) simulated anchor chaining (hereafter referred to as “till”), 3) wetting agent, and 4) till plus wetting agent. Soil water content was highest in the wetting agent treatment, lower for till, and lowest in the control. Overall, the response of bluebunch wheatgrass and cheatgrass was similar among treatments. At the conclusion of the study, wetting agent cores had twice as many seedlings as the control, while the till and control were similar. Despite a lower number of seedlings, tilling in general resulted in the same level of biomass as the wetting agent treatment. Overall, biomass in the till and wetting agent treatments was at least twofold higher than the control. No benefit was found in applying both till and wetting agent treatments together in comparison to just applying wetting agent. Because of a lack of correlation between glasshouse and field settings the results of this study need to be interpreted with caution. Our data may indicate that if cheatgrass is not already present on the site, anchor chaining or treating the soil with wetting agent can increase establishment of seeded species.
Low-power FFT via reduced precision redundancy

We propose a technique for designing low-power fast Fourier transform (FFT) processors with applications in next generation wireless LAN and wireless access systems. The proposed low-power technique is based on the general principle of soft digital signal processing where voltage overscaling (VOS) (scaling the supply voltage beyond the critical voltage V/sub dd-crit/ required for correct operation) is applied in conjunction with algorithmic noise-tolerance (ANT) techniques. We propose an ANT technique referred to as reduced precision redundancy for compensating the degradation in the signal-to-noise ratio (SNR) at an FFT output due to VOS. Simulation results using the proposed scheme with 0.25 /spl mu/m standard CMOS technology show that the power consumption in a butterfly functional unit of an FFT processor can be reduced by 44% over a conventional voltage-scaled system without any SNR loss in the context of a typical orthogonal frequency division multiplexing (OFDM) based WLAN system.
RIM1α phosphorylation at serine-413 by protein kinase A is not required for presynaptic long-term plasticity or learning

Activation of presynaptic cAMP-dependent protein kinase A (PKA) triggers presynaptic long-term plasticity in synapses such as cerebellar parallel fiber and hippocampal mossy fiber synapses. RIM1α, a large multidomain protein that forms a scaffold at the presynaptic active zone, is essential for presynaptic long-term plasticity in these synapses and is phosphorylated by PKA at serine-413. Previous studies suggested that phosphorylation of RIM1α at serine-413 is required for presynaptic long-term potentiation in parallel fiber synapses formed in vitro by cultured cerebellar neurons and that this type of presynaptic long-term potentiation is mediated by binding of 14-3-3 proteins to phosphorylated serine-413. To test the role of serine-413 phosphorylation in vivo, we have now produced knockin mice in which serine-413 is mutated to alanine. Surprisingly, we find that in these mutant mice, three different forms of presynaptic PKA-dependent long-term plasticity are normal. Furthermore, we observed that in contrast to RIM1α KO mice, RIM1 knockin mice containing the serine-413 substitution exhibit normal learning capabilities. The lack of an effect of the serine-413 mutation of RIM1α is not due to compensation by RIM2α because mice carrying both the serine-413 substitution and a RIM2α deletion still exhibited normal long-term presynaptic plasticity. Thus, phosphorylation of serine-413 of RIM1α is not essential for PKA-dependent long-term presynaptic plasticity in vivo, suggesting that PKA operates by a different mechanism despite the dependence of long-term presynaptic plasticity on RIM1α.
Landmark-free posture invariant human shape correspondence

We consider the problem of computing accurate point-to-point correspondences among a set of human bodies in varying postures using a landmark-free approach. The approach learns the locations of the anthropometric landmarks present in a database of human models in strongly varying postures and uses this knowledge to automatically predict the locations of these anthropometric landmarks on a newly available scan. The predicted landmarks are then used to compute point-to-point correspondences between a rigged template model and the newly available scan.
Proprotein convertases in high-density lipoprotein metabolism

The proprotein convertase subtilisin/kexins (PCSKs) are a serine endopeptidase family. PCSK members cleave amino acid residues and modulate the activity of precursor proteins. Evidence from patients and animal models carrying genetic alterations in PCSK members show that PCSK members are involved in various metabolic processes. These studies further revealed the molecular mechanism by which genetic alteration of some PCSK members impairs normal molecular and physiological functions, which in turn lead to cardiovascular disease. High-density lipoprotein (HDL) is anti-atherogenic as it removes excessive amount of cholesterol from blood and peripheral tissues. Several PCSK members are involved in HDL metabolism. PCSK3, PCSK5, and PCSK6 process two triglyceride lipase family members, endothelial lipase and lipoprotein lipase, which are important for HDL remodeling. Recent studies in our lab found evidence that PCSK1 and PCSK9 are also involved in HDL metabolism. A mouse model carrying an amino acid substitution in PCSK1 showed an increase in serum apolipoprotein A1 (APOA1) level. Another mouse model lacking PCSK9 showed a decrease in APOE-containing HDL. In this review, we summarize the role of the five PCSK members in lipid, glucose, and bile acid (BA) metabolism, each of which can influence HDL metabolism. We propose an integrative model in which PCSK members regulate HDL metabolism through various molecular mechanisms and metabolic processes and genetic variation in some PCSK members may affect the efficiency of reverse cholesterol transport. PCSK members are considered as attractive therapeutic targets. A greater understanding of the molecular and physiological functions of PCSK members will improve therapeutic strategies and drug efficacy for cardiovascular disease where PCSK members play critical role, with fewer adverse effects.
Application of New Concepts in Cell-Mediated Immunity to the Development of Effective Antifertility Vaccines

A successful antifertility vaccine, based on β-HCG (human chorionic gonadotropin), sperm, or other reproductive-tissue-specific antigens, must elicit an immune response which effectively achieves an antifertility effect. A major problem facing antifertility-vaccine development is the fact that reproductive-tissue antigens are weak immunogens; most vaccine studies to date, in both animal models and human phase I clinical trials, have failed to produce a sustained antibody response and/or the desired antifertility effect.
The head arterial glucose level is not the reference site for generation of the portal signal in conscious dogs

Experiments were performed on twelve 42-h-fasted, conscious dogs to determine whether the head arterial glucose level is used as a reference standard for comparison with the portal glucose level in...
Heat transfer in plagioclase feldspars

Laser-flash analyses (LFA) of oriented sections of six natural plagioclase crystals provide thermal diffusivity ( D ) as function of temperature (to ~1300–1500 K) and composition (An5–95). Plagioclase has low-thermal diffusivity; our measurements indicate that plagioclase is more insulating than other major igneous rock-forming minerals. Over much of the solid solution, room-temperature D ranges from 0.751 to 0.979 mm2/s along c , 0.722 to 0.919 mm2/s along b , and 0.632 to 0.868 mm2/s perpendicular to b and c . The directionally averaged D is 30–45% lower than D of Amelia albite. Thermal conductivities calculated using measured D values are almost the same for all samples with 18 ≤ An ≤ 65, ranging from 1.5 to 1.9 W/m/K and changing little with temperature. Increasing Al-Si disorder causes D to decrease with increased An content, although sample structure causes more ordered samples to have higher D than more disordered samples. Anorthite is a special case. Although ordered, the larger unit cell provides many lattice modes, leading to low diffusivity. Structure dictates whether D along the b -axis is greater or less than that along the c -axis, possibly because ordering in An-like domains increases D more along c relative to b . Inflections in 1/ D ( T ) are connected with lattice distortion during heating, and occur near temperatures expected for phase transitions; for example, the lattice stretch occurring at the temperature of the transition to C 1 structure lowers diffusivity. Likewise, lattice distortion during heating decreases D in albite along c but has little impact on D in the other directions. The anharmonic lattice effects that dictate both thermal expansivity and D are masked by effects of disorder; the latter plays a major role in heat transport in plagioclase.
New mouse model for studying laryngeal transplantation.

Objectives: Laryngeal transplantation research has been studied in various animal models. For in-depth, immunology-based transplantation research, however, a thoroughly studied animal model must exist. The purpose of this study was to develop a reliable surgical technique in mice to serve as a model for further study of laryngeal transplantation. Methods: Heterotopic laryngeal transplantation was attempted in 15 immunocompetent mice by use of modifications of previously described techniques established in rats. Results: Various microvascular techniques were used that led to 8 successful transplants (of 15) with patent vascularity at the time of sacrifice. The first 7 attempts at transplantation were unsuccessful because of technical difficulties related to vessel size, soft tissue traumatic injury, and venous congestion. Subsequently, 8 transplantation procedures were successfully performed after modifications of the surgical technique. Conclusions: This pilot study describes the reproducible surgical techniques performed in using mice for studying laryngeal transplantation. Mice are cost-effective and immunologically well studied, and are thus ideal for further laryngeal transplantation research.
Changes in fermentation and biohydrogenation intermediates in continuous cultures fed low and high levels of fat with increasing rates of starch degradability

Excessive levels of starch in diets for lactating dairy cattle is a known risk factor for milk fat depression, but little is known about how this risk is affected by differences in rates of starch degradability (Kd) in the rumen. The objective of this study was to compare accumulation of biohydrogenation intermediates causing milk fat depression, including conjugated linoleic acid (CLA), when corn with low or high Kd were fed to continuous cultures. Diets contained (dry matter basis) 50% forage (alfalfa pellets and grass hay) and 50% concentrate, with either no added fat (LF) or 3.3% added soybean oil (HF). Within both the LF and HF diets, 3 starch degradability treatments were obtained by varying the ratio of processed (heat and pressure treatments) and unprocessed corn sources, giving a total of 6 dietary treatments. Each diet was fed to dual-flow continuous fermenters 3 times a day at 0800, 1600, and 2400h. Diets were fed for four 10-d periods, with 7d for adaptation and 3d for sample collection. Orthogonal contrasts were used in the GLIMMIX procedure of SAS to test the effects of fat, starch degradability, and their interaction. Acetate and acetate:propionate were lower for HF than for LF but daily production of trans-10 18:1 and trans-10,cis-12 CLA were higher for HF than for LF. Increasing starch Kd from low to high increased culture pH, acetate, and valerate but decreased butyrate and isobutyrate. Changes in biohydrogenation intermediates (expressed as % of total isomers) from low to high starch Kd included reductions in trans-11 18:1 and cis-9,trans-11 CLA but increases in trans-10 18:1 and trans-10,cis-12 CLA. The results show that increasing the starch Kd in continuous cultures while holding starch level constant causes elevation of biohydrogenation intermediates linked to milk fat depression.
Molecular Events in Axonal Regeneration

We consider whether a neuron must alter its program of gene expression in order to regenerate an injured axon. We conclude that certain information required for axon growth is encoded in the normal constituents of a quiescent axon, and certain aspects of axon growth may be regulated by environmental information impinging directly on the normal constituents of the axon. However, successful axon regeneration requires the introduction into the axon of a small number of new gene products that perform growth-specific functions. Because mammalian CNS neurons do not express these growth-related genes after axonal injury, their failure to regenerate their axons may be a consequence of the inability of the CNS to accomplish one of the steps in the sequence that leads from axon injury to the expression of growth-related genes.
Whirlwinds and Hairpins in the Atmospheric Surface Layer

AbstractVortices in the atmospheric surface layer are characterized using observations at unprecedented resolution from a fixed array of 31 turbulence sensors. During the day, these vortices likely are dust devils, though no visual observations are available for confirmation. At night, hairpin vortices appear to have been observed. The structure and dynamics of several types of vortices are described and related to other vortex investigations, including tornadoes and hurricanes.
Computing Arithmetic Functions Using Stochastic Logic by Series Expansion

Stochastic logic implementations of complex arithmetic functions, such as trigonometric, exponential, and sigmoid, are derived based on truncated versions of their Maclaurin series expansions. This paper makes three contributions. First, it is shown that a polynomial can be implemented using multiple levels of NAND gates based on Horner’s rule, if the coefficients are alternately positive and negative and their magnitudes are monotonically decreasing. Truncated Maclaurin series expansions of arithmetic functions are used to generate polynomials which satisfy these constraints. The input and output in these functions are represented by unipolar representation. Functions including sine, cosine, tangent hyperbolic, logarithm and exponential can be implemented using this method. Second, for a polynomial that does not satisfy these constraints, it still can be implemented based on Horner’s rule if each factor of the polynomial satisfies these constraints. It is shown that functions such as $\sin \pi x/\pi$ , $e^{-ax}$ , $\tanh ax$ and $\text{sigmoid}(ax3)$ (for values of $a>1$ ) can be implemented using stochastic logic using factorization in combination with Horner’s rule. Third, format conversion is proposed for arithmetic functions with input and output represented in different formats, such as $\text{cos}\,\pi x$ given $x\in [0,1]$ and $\text{sigmoid(x)}$ given $x\in [-1,1]$ . Polynomials are transformed to equivalent forms that naturally exploit format conversions. The proposed stochastic logic circuits outperform the well-known Bernstein polynomial based and finite-state-machine (FSM) based implementations. Furthermore, the hardware complexity and the critical path of the proposed implementations are less than the well-known Bernstein polynomial based and FSM based implementations for most cases.
Graphic Depictions: Portrayals of Mental Illness in Video Games.

Although studies have examined portrayals of mental illness in the mass media, little attention has been paid to such portrayals in video games. In this descriptive study, the fifty highest-selling video games in each year from 2011 to 2013 were surveyed through application of search terms to the Wikia search engine, with subsequent review of relevant footage on YouTube. Depiction categories were then assigned based on the extent of portrayal and qualitative characteristics compared against mental illness stereotypes in cinema. Twenty-three of the 96 surveyed games depicted at least one character with mental illness. Forty-two characters were identified as portraying mental illness, with most characters classified under a “homicidal maniac” stereotype, although many characters did not clearly reflect cinema stereotypes and were subcategorized based on the shared traits. Video games contain frequent and varied portrayals of mental illness, with depictions most commonly linking mental illness to dangerous and violent behaviors.
Identification of anomalies in lane change behavior using one-class SVM

Advanced driver assistance systems are required to detect latent hazards posed by surrounding vehicles and generate an appropriate response to enhance safety. Lane changes constitute potentially risky maneuvers, as drivers involved encounter latent hazards due to surrounding vehicles. A careful study of lane change behavior is therefore essential in identifying potential abnormalities that may lead to various hazards, during the process of a lane change. In this study, an anomaly detection technique is used to compare snapshots of normal and dangerous lane change maneuvers, to identify the abnormal instances. A one-class support vector machine is used and tested for novelty identification of naturalistic driving study data. The results show that the technique is able to detect dangerous lane changes with high accuracy. In addition, results suggest that dangerous behavior could occur before, after or during a lane change maneuver.
CRYOBALLOON VERSUS RADIOFREQUENCY ABLATION OF ATRIAL FIBRILLATION: IN-LAB COMPLICATION RATES AT A LARGE VOLUME ELECTROPHYSIOLOGY CENTER

Background: Left atrial catheter ablation is a curative option for patients with symptomatic atrial fibrillation (AF). Focal radiofrequency (RF) and circumferential cryothermal energy balloon (CB) remain the most commonly used energy delivery techniques, yet subsequent in-lab complication rates are
Ecological Change Drives a Decline in Mercury Concentrations in Southern Beaufort Sea Polar Bears

We evaluated total mercury (THg) concentrations and trends in polar bears from the southern Beaufort Sea subpopulation from 2004 to 2011. Hair THg concentrations ranged widely among individuals from 0.6 to 13.3 μg g–1 dry weight (mean: 3.5 ± 0.2 μg g–1). Concentrations differed among sex and age classes: solitary adult females ≈ adult females with cubs ≈ subadults > adult males ≈ yearlings > cubs-of-the-year ≈ 2 year old dependent cubs. No variation was observed between spring and fall samples. For spring-sampled adults, THg concentrations declined by 13% per year, contrasting recent trends observed for other Western Hemispheric Arctic biota. Concentrations also declined by 15% per year considering adult males only, while a slower, nonsignificant decrease of 4.4% per year was found for adult females. Lower THg concentrations were associated with higher body mass index (BMI) and higher proportions of lower trophic position food resources consumed. Because BMI and diet were related, and the relationship to ...
Investigating an Incentive-Sensitization Model of Eating Behavior: Impact of a Simulated Fast-Food Laboratory:

The incentive-sensitization (IS) theory proposes that “wanting” (strong motivation), more so than “liking” (hedonic pleasure), drives compulsive consumption in both substance use and overeating. Importantly, “wanting” and “liking” are only distinct in the presence of relevant cues. Cues may also contribute to overeating by increasing feelings of hunger. We employed a simulated fast-food laboratory to test IS theory by examining the effect of environmental cues on eating behavior. We tested the following hypotheses: In a cue-rich compared to neutral environment, (a) wanting would be greater whereas liking would remain the same, (b) feelings of hunger would be greater, and (c) food consumption would be greater, a relationship mediated by elevated wanting and hunger. These hypotheses were supported in the current study. Thus, contextual cues may contribute to overconsumption through increased wanting and hunger. These findings have public health implications for overeating and obesity.
Financial Impact of Acute Kidney Injury After Cardiac Operations in the United States

Background Acute kidney injury (AKI) after major cardiac operations is a potentially avoidable complication associated with increased morbidity, death, and costly long-term treatment. The financial impact of AKI at the population level has not been well defined. We sought to determine the incremental index hospital cost associated with the development of AKI. Methods All patients undergoing coronary artery bypass grafting (CABG) or valve replacement operations, or both (clinical classification software codes 43 and 44), between 2008 and 2011 were identified from the Nationwide Inpatient Sample. AKI was identified using International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes (584.xx); patients with chronic renal failure were excluded. Mean total index hospitalization costs were compared between patients with and without AKI. Results At the population level, 1,078,036 individuals underwent major cardiac procedures from 2008 to 2011, with AKI developing in 105,648 (9.8%). Specifically, AKI developed in 8.0% of CABG, 11.4% of valve replacement, and 17.0% of CABG plus valve replacement patients ( p p p Conclusions AKI developed in 1 in every 10 patients nationwide after a cardiac operation. Achieving a 10% reduction in AKI in this population would likely result in an annual savings of approximately $100,000,000 in index-hospital costs alone. Support for research on mechanisms to detect impending damage and prevent AKI may lead to reduced patient morbidity and death and to substantial health care cost savings.