cssi/SciSciGPT-SciSciNet huggingface dataset:
Horizontal transfer of ATPase genes — the tree of life becomes a net of life

Abstract An ancient gene duplication gave rise to the catalytic and non-catalytic subunits of each of the three types of proton pumping ATPases: vacuolar, archaebacterial and eubacterial. Previously, this gene duplication had been used to root the universal tree of life. However, recent findings of archaebacterial type ATPases in eubacteria and of eubacterial type in an archaebacterium suggested that both types of ATPases may have been already present in the last common ancestor. Here we show that a phylogenetic analysis of these ATPase subunits indicates that this conclusion is premature. We suggest that horizontal gene transfer can explain the data. In addition, we show that the analysis of glutamate dehydrogenases data neither affirm nor contradict any particular placement of the last common ancestor in the universal tree of life. The prevalence and the mode of horizontal gene transfer is discussed.
Broad host range fluorescence and bioluminescence expression vectors for Gram-negative bacteria

Tagging of bacteria with living colors and living light allows increasingly valuable new imaging and detection technologies to be accessible to researchers. In this study, we aimed to create stable broad host range expression vectors for tagging Gram-negative bacteria with fluorescence and bioluminescence. To accomplish this, a mutated form of promoterless green fluorescent protein (gfp) gene, gfpmut3a, from Aequorea victoria and promoterless bacterial luciferase genes, luxCDABE, from Photorhabdus luminescens were inserted into broad host range plasmid pBBR1MCS4. Expression of gfp and luxCDABE genes was driven by lacZ promoter. In addition, dual versions with both gfpmut3a and luxCDABE genes and inducible versions carrying lacI(q) gene were also constructed. These new broad host range vectors containing a stable broad host range origin of replication and mobility genes can be transferred to Gram-negative bacteria by either electroporation or conjugal mating and maintained stably. Availability of these expression vectors should be useful in developing new approaches to study a broad variety of Gram-negative bacteria, particularly for applications investigating host-pathogen interactions in vivo and in vitro.
Fentanyl produces cholinergically-mediated analeptic and EEG arousal effects in rats.

Abstract Fentanyl (20 μg/kg i.p.), administered to naltrexone-pretreated, pentobarbital-anesthetized rats, produced a shortening of the duration of narcosis. This analeptic effect was blocked by atropine, but not by methylatropine, indicating that a central cholinergic mechanism was involved. Fentanyl also increased sodium-dependent high affinity uptake of choline activity in the hippocampus and cortex that had been depressed by the barbiturate. Injection of 0.8 ng of fentanyl into the pontis oralis in the pontine reticular formation also produced analepsis in naltrexone-pretreated, pentobarbitalized rats. Hippocampal EEG recordings also showed the appearance of cholinergically-mediated theta activity, which was indicative of arousal activity in the hippocampus. These results suggest that fentanyl, in addition to possessing potent opiate activity, also activates a nonopioid-mediated central cholinergic arousal system.
Development of Life Prediction Method of Turbine Blade Using the Theory of Critical Distance

Gas turbine blades mounted dovetail root are subjected to high centrifugal loads and gas forces. This situation causes low cycle fatigue (LCF). Recently, rotating speed and temperature of turbine rotor become higher in order to improve engine performance. To achieve this, it is required to evaluate accurate turbine blade’s LCF life of the contact surface between the blade dovetail root and the disk. However, the estimated blade lives using the peak stress calculated by finite element analysis (FEA) are much shorter than actual life because the stress at contact surface is excessively high. As a result, the blades are designed conservative and the blade’s weight tends to be heavy. Therefore, a more accurate evaluation methodology needs to be established.This study investigates the method to estimate the fatigue strength of dovetail using the theory of critical distance. The theory assumes that fatigue failures would occur due to the representative stress within a specific distance from stress concentration point. Fatigue tests and FEA for the turbine blade dovetail were conducted respectively in this research. The tests were carried out using single crystal nickel-based turbine blades at 600 °C and the fracture lives of dovetail were obtained. FEA was conducted to obtain the stress distributions at dovetail contact surface under testing condition. In this study, the critical distances of the single crystal nickel based alloy were obtained from the notched bar fatigue tests and FEA. Using these results and the theory of critical distance, fatigue lives of dovetail were obtained more accurately.© 2012 ASME
Acceleration Feedback Control of MDOF Structures

To date, most of the current active structural control strategies for aseismic protection have been based on either full-state feedback (i.e., all structural displacements and velocities) or on velocity feedback. However, accurate measurement of displacements and velocities is difficult to achieve directly in full-scale applications, particularly during seismic activity, since the foundation of the structure is moving with the ground. Because accelerometers can readily provide reliable and inexpensive measurement of accelerations at strategic points on the structure, development of control methods based on acceleration feedback is an ideal solution to this problem. The purpose of the present paper is to demonstrate experimentally that acceleration feedback-control strategies are effective and robust, and they can achieve performance levels comparable to full-state feedback controllers.
Depression in Asian-American and Caucasian undergraduate students.

Abstract Background Depression is a serious and often under-diagnosed and undertreated mental health problem in college students which may have fatal consequences. Little is known about ethnic differences in prevalence of depression in US college campuses. This study compares depression severity in Asian–American and Caucasian undergraduate students at the University of California San Diego (UCSD). Methods Participants completed the nine item Patient Health Questionnaire and key demographic information via an anonymous online questionnaire. Results Compared to Caucasians, Asian–Americans exhibited significantly elevated levels of depression. Furthermore, Korean–American students were significantly more depressed than Chinese–American, other minority Asian–American, and Caucasian students. In general, females were significantly more depressed than males. Results were upheld when level of acculturation was considered. Limitations The demographic breakdown of the student population at UCSD is not representative to that of the nation. Conclusions These findings suggest that outreach to female and Asian–American undergraduate students is important and attention to Korean–American undergraduates may be especially worthwhile.
SU-E-J-114: Towards Integrated CT and Ultrasound Guided Radiation Therapy Using A Robotic Arm with Virtual Springs

Purpose: Currently there is an urgent need in Radiation Therapy for noninvasive and nonionizing soft tissue target guidance such as localization before treatment and continuous monitoring during treatment. Ultrasound is a portable, low cost option that can be easily integrated with the LINAC room. We are developing a cooperatively controlled robot arm that has high intrafraction reproducibility with repositioning of the ultrasound probe. In this study, we introduce virtual springs (VS) to assist with interfraction probe repositioning and we compare the soft tissue deformation introduced by VS to the deformation that would exist without them. Methods: Three metal markers were surgically implanted in the kidney of one dog. The dog was anesthetized and immobilized supine in an alpha cradle. The reference ultrasound probe position and force to ideally visualize the kidney was defined by an experienced ultrasonographer using the Clarity ultrasound system and robot sensor. For each interfraction study, the dog was removed from the cradle and re-setup based on CBCT with bony anatomy alignment to mimic regular patient setup. The ultrasound probe was automatically returned to the reference position using the robot. To accommodate the soft tissue anatomy changes between each setup the operator used the VS feature tomore » adjust the probe and obtain an ultrasound image that matched the reference image. CBCT images were acquired and each interfraction marker location was compared with the first interfraction Result. Results: Analysis of the marker positions revealed that the kidney was displaced by 18.8 ± 6.4 mm without VS and 19.9 ± 10.5 mm with VS. No statistically significant differences were found between two procedures. Conclusion: The VS feature is necessary to obtain matching ultrasound images, and they do not introduce further changes to the tissue deformation. Future work will focus on automatic VS based on ultrasound feedback. Supported in part by: NCI R01 CA161613; Elekta Sponsored Research.« less
Humeral head replacement versus total shoulder arthroplasty: Clinical outcomes—a review

Total shoulder replacement (TSR) has been shown to provide predictable pain relief and functional improvement in patients with glenohumeral degenerative arthritis and an intact rotator cuff. When compared with patients with humeral head replacement (HHR), those with TSR have been reported to have more stability, less pain, and increased motion. However, concerns regarding glenoid loosening and the subsequent possibility of a difficult revision with bony deficits have led many to favor HHR alone. Proponents of HHR regard the glenoid as the "weak link" in TSR and, when weighing their options, consider glenoid resurfacing to be too great a risk. The literature suggests that TSR is the best form of treatment for glenohumeral osteoarthritis, except in certain cases of insufficient glenoid bone stock and irreparable rotator cuff tears. Several recent clinical outcomes studies support this, as they have shown better results after TSR in comparison to HHR. Although the fear of radiographic glenoid component loosening is appropriate, evidence of clinical glenoid loosening is not very common. Currently, glenoid component design, in relation to its articulation with the humeral head, continues to grow and evolve as efforts are focused on changes to decrease the incidence of loosening. In addition, improved surgical techniques of cement pressurization may help to minimize glenoid loosening as well. Thus, it is reasonable to expect that the excellent results currently attainable with TSR may improve.
Reproduction In Vitro of a Quasispecies from a Hepatitis C Virus-Infected Patient and Determination of Factors That Influence Selection of a Dominant Species

Hepatitis C virus infections proceed to chronicity in the majority of cases. In patients, hepatitis C viruses exist as a dynamic and complex quasispecies. The dominant species at any one time arises in response to host immune pressure and other, incompletely understood factors. It is critical to understand all the mechanisms by which dominance is achieved, but this is difficult to study in vivo. Therefore, it would be useful to develop a cell culture system in which naturally occurring quasispecies could be studied. Hepatitis C virus glycoprotein genes E1 and E2 were PCR amplified as a cassette from the plasma of a chronically infected patient and shotgun cloned into a modified 1a/JFH1 infectious cDNA clone. Following transformation of bacteria, plasmids were batch harvested, transcribed, and transfected into Huh7.5 cells to produce a quasispecies of hypervariable region 1 (HVR1) that mimicked that circulating in vivo. Serial passage of the quasispecies in vitro resulted in replacement of the initially dominant species with a new HVR1 species coexisting with selected growth-enhancing mutations located outside HVR1. Antibody raised against one HVR1 sequence neutralized virus with the homologous HVR1 and cross-neutralized virus with a different sequence. Reciprocal swapping of the HVR1 regions between the two dominating species demonstrated that the HVR1 sequence affects the efficiency of replication and of neutralization by anti-HVR1 but that both processes are strongly influenced by regions outside HVR1.
Toward Exercise as Personalized Medicine

The early 21st century has witnessed a steady push by scientists, industry leaders, and government officials to make medicine more personalized. To date, the concept of personalized medicine has referred largely to the field of pharmacogenomics. In contrast, relatively few data exist regarding the application of preventive strategies such as physical exercise in the context of personalized medicine. Within this review, we highlight the extant literature and propose five strategies for scientists that may propel the exercise and sports science fields toward this global goal. Notably, these approaches are in addition to methods to maintain adherence to training – a well-known factor in determining exercise responsiveness. Briefly, these strategies include (1) evaluating participant responses to training at the individual as well as group level; (2) identifying sources of variability in responsiveness to training; (3) optimizing exercise dosing strategies to maximize benefits while minimizing barriers to participation; (4) evaluating the efficacy of multimodal interventions for relevant population subgroups; and (5) increasing the clinical relevance of study populations and outcomes in exercise trials. We look forward to seeing these strategies considered in trials of preventive health interventions such as exercise. Extensive future research in this area is needed for the vision of exercise as a personalized form of medicine to become a reality.
Comparative study of metallic and dielectric helix photonic metamaterial

We compare the performance of metallic and dielectric thin film helix photonic metamaterial numerically. The simulated metal helix provides a 4 μm broad band circular dichroism with a polarization suppression ratio of 20:1. The transmission efficiency of the metal helix drops significantly with increasing number of helix turns and angle of incidence. Contraire, the simulated silicon dielectric helix structure provides an extremely high polarization suppression ratio above 2,300:1 with almost 100% transmission over a wide range of incident angles. The results provided highlights the trade-offs between the transmission efficiency and the specular and angular bandwidth for designing practical thin-film circular polarizers.
Rapid publication a chromogranin a‐derived peptide differentially regulates the secretion of calcitonin gene products

We studied the regulation of the secretion of CT and CGRP by chromogranin A (CgA)-derived peptides in a human lung tumor cell line. The amino-terminal peptide of CgA, CgA1-40, stimulated the secretion of CGRP and inhibited the secretion of CT; both effects occurred in a dose-dependent manner. These studies demonstrate a differential effect of a CgA-derived peptide on two products of the CT gene, CT itself and CGRP. CgA may be processed at its multiple dibasic sites to peptides that specifically regulate the secretion of its coresident hormones, in this case two calcitonin gene products that are present in the same secretory vesicle. This novel mechanism represents a new pathway for the control of calcium regulating hormones.
Sarcomas near extremity joints in adults

Background and Objectives: There are technical difficulties in resecting soft tissue sarcomas extending to or crossing a joint. The objective of this study was to determine the rate of amputation and local recurrence rate for these sarcomas and compare them with the respective rates for overall extremity sarcomas. Methods: Retrospective review of 78 patients with sarcoma near a joint compared with 215 patients with extremity sarcomas accrued during the same period, 1977-1994. Of these 78 patients, 64 were in the lower and 14 in the upper extremity. Most common histologic subtypes were malignant fibrous histiocytoma (15/78, 19%), synovial sarcoma (11/78, 14%), liposarcoma (11/78, 14%), and leiomyosarcoma (10/78, 13%). The surgical treatment consisted of local excision in 10 (13%), wide excision in 56 (72%), and amputation in 12 (15%). Adjuvant radiation was given to 26 patients. Results: Local recurrence was noted in 20% (16/78) patients. The incidence of local recurrence in the surgery alone group (n = 52) was 15% (8/52) and in the surgery plus adjuvant radiation group (n = 26) it was 31% (8/26); P = 0.11. Of the 16 patients with local recurrence, 9 (56%) required amputation. The 5-year and 10-year survival rates for the entire group of patients were 68% and 60% respectively. On multivariate analysis survival varied according to grade (P = 0.05) and tumor size (P = 0.02). Conclusions: Amputation was finally required in 27% (21/78) for local control of the disease. The local recurrence rate was 20%. These rates appear to be somewhat higher than those reported in our overall extremity sarcoma series and those in most modern series of overall extremity sarcomas, but the 5- and 10-year survival rates are similar to those of the latter.
Anisotropic Aggregate Base Inputs for Mechanistic Pavement Analysis Considering Effects of Moving Wheel Loads

A new methodology is presented in this paper for determining cross-anisotropic aggregate base properties, i.e., directional dependency of moduli and Poisson's ratios, as inputs into mechanistic pavement analysis considering effects of actual traffic or moving wheel loading. The proposed materials characterization requires conducting constant stress path triaxial tests and incrementally varying loading stress path slopes at similar stress states that are representative of various moving wheel loading conditions in the laboratory. In accordance, cross-anisotropic aggregate properties are determined by varying slightly the stress path slopes during testing and then by employing an error minimization approach to interpret the test results. Crushed aggregate specimens were prepared and tested to obtain cross-anisotropic properties at five different stress path slopes representative of various moving wheel load induced compression and extension type pavement stress states. Vertical resilient moduli were commonly found to be larger than horizontal ones and critically low resilient moduli were also obtained for some extension states. The findings point to advances needed in granular materials characterization such as incorporating anisotropic and stress dependent behavior into mechanistic pavement analysis and properly considering the effects of moving wheel loading on pavement response.
Spatial location memory discriminates children born at extremely low birth weight and late-preterm at age three.

Objective: The spatial location memory of preschool-aged children born preterm has rarely been studied primarily due to an absence of developmentally sensitive measures. This study aimed to address this gap in the literature. Method: We administered a modification of the Hopkins Board to 135 children at age 3 who were born extremely low birth weight (ELBW) (n = 20), late-preterm (LPT) (n = 75), or at term (TERM) (n = 40). Five measures were obtained: naming, trials-to-criterion, errors-to-criterion, delayed item recall, and delayed location recall. Results: ANCOVA indicated that the groups differed in naming (p = .019), errors-to-criterion (p = .002), and delayed item recall (p = .025). For these measures, ELBW performed worse than TERM and LPT, but LPT did not differ from TERM. Corrected age and sociodemographic factors did not eliminate the deficit in spatial location learning for ELBW participants. A MANCOVA found a significant difference in learning, with post hoc tests indicating significant learning across trials in the LPT and TERM groups, but not in the ELBW group. Conclusions: ELBW is a significant risk factor for developmental delay or impairment of spatial location learning. These findings suggest that the modified Hopkins Board identifies at-risk premature children. This modification may be more broadly useful to assess preschoolers' neurodevelopmental maturation.
DMSA chelation during co-exposure to lead: Increased locomotor activity in lead-exposed mice but not controls

We investigated the effect of chelating agent meso-2,3 dimercaptosuccinic acid (DMSA) on indices of "hyperactive" behavior in lead-exposed and control Binghamton Heterogeneous Stock (Het) mice. As expected, 6 weeks of ingestion of 0.5% lead acetate in drinking water reduced immobility in a forced water swim relative to controls. DMSA did not attenuate this behavioral change. In fact, DMSA interacted with lead exposure to increase locomotor activity in the forced water swim. DMSA also apparently excacerbated lead's tendency to reduce immobility. While any generalizations to human populations should be cautioned, these results and others suggest the need for further research.
The slightly-rough facet model in radar imaging of the ocean surface

Abstract The slightly-rough facet model of the ocean surface, an extension of the two-scale radar scattering model, is well suited for investigating synthetic aperture radar (SAR) imaging of the surface. We derive several statistical properties of the facets that are important in an imaging model. The two-scale scattering model is extended to include both first-order and second-order large-scale effects (tilt and curvature) using physical optics, showing that a spectrum of small-scale ripples, rather than a single ripple given by the Bragg resonance condition, contributes to the backscatter from a facet. The bandwidth of the resonant ripple spectrum depends on the radar wavelength, large-scale curvature and illumination widths. The properties of the facets are deduced from this dependence. The large-scale curvature of the surface determines the size of the facets. The expected facet size depends directly on the radar wavelength and is much smaller than the resolution of realistic radars. The resonant ripp...
Role of novelty in the aversion for increasingly concentrated saccharin solutions

Abstract In Experiment 1, the role of novelty in the aversion response to increasingly concentrated flavored solutions was determined by repeatedly testing independent groups with 0.15, 0.5, 1.0, 2.0, and 3.0% saccharin. Initially, intakes quickly declined with increasing saccharin concentrations. However, animals drank more as they gained familiarity with the saccharin flavors, and their aversion to the more concentrated solutions became considerably attenuated. In Experiment 2, each animal was tested with 0.15, 0.5, 1.0, 2.0, and 3.0% saccharin in an irregular order following training with one of the saccharin solutions. Animals extensively familiarized with the high saccharin concentrations prior to the test sessions showed much less aversion to these solutions than animals for which the high saccharin concentrations were novel. These results demonstrate that the aversion response to increasingly concentrated flavored solutions is in part a function of the relative novelty of the flavors, and suggest that adequate control of relative novelty is necessary in studies of other variables regulating intake.
Anterior Instability of the Shoulder: Effect of Arm Position and Relative Contributions of Bony Bankart and Hill-Sachs Defects

Shoulder stability can be significantly reduced in the presence of bony defects. Bony Bankart and Hill-Sachs lesions are known causes for recurrent shoulder dislocation. It has been shown in literature that often these defects are present together during cases of recurrent dislocation.1 However, past studies have only analyzed the effects of isolated bony Bankart or Hill-Sachs lesions.2, 3 Recent studies have stated that a Hill-Sachs lesion that “engages” the anterior glenoid has a critical impact on shoulder stability.4 It is important to understand the relationship between these two bony defects, as this would lead to better management of the shoulders’ instability.Copyright © 2013 by ASME
Extending the R-2R lens to 360&#176;

The R.2R lens is a remarkable microwave device that provides perfect focusing, giving multiple simultaneous antenna beams from a circular or cylindrical array. However, the perfect focusing of the R-2R brings with it a serious limitation on angular coverage as a result of the angular doubling that enters when the array elements in the antenna are connected to the launcher elements on the lens periphery. We have now found a way to modify the R-2R concept so that a full circle of array elements can be mapped onto a full circle of beam ports. The new mapping makes use of hybrid junctions and either four or six physical lenses. The interconnections result in 360\deg of simultaneous antenna beams, each of which can be used both for transmission and for reception.
Management of giant middle cerebral artery aneurysms with incorporated branches: partial endovascular coiling or combined extracranial-intracranial bypass--a team approach.

Objective Our goal was to assess the long-term anatomic and clinical outcomes in patients with giant middle cerebral artery (MCA) aneurysms treated by endovascular coil embolization alone or in combination with cerebral revascularization. Methods One hundred twenty-six patients with giant intracranial aneurysms were endovascularly treated at the University of California, Los Angeles, between 1990 and 2007. Of these, 9 patients had partially thrombosed MCA aneurysms with incorporated branches. Five patients presented with symptoms of mass effect, 3 had seizures, 2 had episodes of brain ischemia, and 1 presented with acute subarachnoid hemorrhage. Results Three wide-neck saccular aneurysms were almost completely coil occluded, leaving only small neck remnants that were intended to preserve the patency of incorporated MCA branches. The other 6 fusiform aneurysms were effectively treated by superficial temporal artery-MCA or occipital artery-MCA bypass, followed by complete coil occlusion of these aneurysms. Immediate angiograms and mid- or long-term neuroradiological imaging follow-up examinations revealed complete obliteration or near-complete occlusion (90%-99%) of the aneurysms in all 9 patients. Seven patients had a favorable long-term clinical outcome, and 1 patient died as a result of unrelated congestive heart failure. One patient required emergent surgical aneurysm thrombectomy because of inadvertent coil occlusion of the frontal opercular artery, which was not protected by the bypass, and the patient subsequently sustained a moderate neurological disability. Conclusion Giant MCA aneurysms with branch incorporations and other unfavorable features such as intraluminal thrombus, mural calcification, and fusiform configuration can be effectively treated with a team approach, using coil embolization after protective surgical bypass. When aneurysms with MCA branches incorporated into the neck rather than the dome are treated by endovascular techniques alone, long-term angiographic follow-up is necessary to assess and further treat any significant remnant.
Solidification on a substrate

Abstract Most currently used rapid solidification techniques (such as melt spinning, melt extraction, melt drag, planar flow casting, double anvil, hammer and anvil and splat quenching) are simple variants on a common theme. Molten metal is brought into contact with a cool substrate, usually metallic. The molten metal forms a bond with the substrate, permitting heat to be transferred rapidly across the bond interface into the substrate. At some stage the bond is broken and the casting separates from the substrate. Bond formation behavior is very similar to that of adhesion in sliding friction. On this basis, the bond formation, the forces involved in breaking the bond and the role of the substrate surface chemistry, geometry and temperature are discussed. A simplified melt-drag system has been developed and used to study the role of various solidification parameters, particularly heat transfer. This study has made it possible to demonstrate experimentally the validity of some aspects of the proposed model of solidification on a substrate.
Cochlear abnormalities associated with enlarged vestibular aqueduct anomaly.

Abstract Objectives The objective of this study is to examine the correlation between enlarged vestibular aqueduct (EVA) anomaly and other inner ear anomalies such as cochlear dysplasia, vestibulocochlear dysplasia and modiolar hypoplasia. Methods Retrospective chart review, with institutional review board approval, of patients with EVA who received treatment at Primary Children's Medical Center or University Hospital at the University of Utah, between 1997 and 2006. Review of radiographs was done to evaluate for the presence of EVA and other inner ear anomalies. Results Twenty patients (40 ears) were included in the study, 17 patients had bilateral EVA and three patients had unilateral EVA. There were 10 females and 10 males. The average age of all patients at the time of initial diagnosis was 1.7 years (0–6 years). Thirty-seven ears were shown to have EVA (92.5%). Of those ears with EVA, 29 (78.4%) had one or more inner ear anomalies. Twenty-three (62.2%) ears had cochlear dysplasia, six (16.2%) had vestibulocochlear dysplasia, and 18 (48.7%) had modiolar hypoplasia. Conclusions Using small field of view, thin section CT and/or MR imaging, cochleovestibular abnormalities are commonly identified in association with EVA.
Verification of a novel NADH-binding motif: Combinatorial mutagenesis of three amino acids in the cofactor-binding pocket of Corynebacterium 2,5-diketo-D-gluconic acid reductase

A screening method has been developed to support randomized mutagenesis of amino acids in the cofactor-binding pocket of the NADPH-dependent 2,5-diketo-D-gluconic acid (2,5-DKG) reductase. Such an approach could enable the isolation of an enzyme that can better catalyze the reduction of 2,5-DKG to 2-keto-L-gulonic acid (2-KLG) using NADH as a cofactor. 2-KLG is a valuable precursor to ascorbic acid, or vitamin C, and an enzyme with increased activity with NADH may be able to improve two potential vitamin C production processes. Previously we have identified three amino acid residues that can be mutated to improve activity with NADH as a cofactor. As a pilot study to show feasibility, a library was made with these three amino acids randomized, and 300 random colonies were screened for increased NADH activity. The activities of seven mutants with apparent improvements were verified using activity-stained native gels, and sequencing showed that the amino acids obtained were similar to some of those already discovered using rational design. The four most active mutants were purified and kinetically characterized. All of the new mutations resulted in apparent kcat values that were equal to or higher than that of the best mutant obtained through rational design. At saturating levels of cofactor, the best mutant obtained was almost twice as active with NADH as a cofactor as the wild-type enzyme is with NADPH. This screen is a valuable tool for improving 2,5-DKG reductase, and it could easily be modified for improving other aspects of this protein or similar enzymes.
What computer architects need to know about memory throttling

Memory throttling is one technique for power and energy management that is currently available in commercial systems, yet has has received little attention in the architecture community. This paper provides an overview of memory throttling: how it works, how it affects performance, and how it controls power. We provide measured power and performance data with memory throttling on a commercial blade system, and discuss key issues for power management with memory throttling mechanisms.
Medullary cells of origin of vagal cardioinhibitory fibers in the pigeon. II. Electrical stimulation of the dorsal motor nucleus.

Stimulation of the peripheral end of the cervical vagus results in marked bradycardia, a secondary fall in blood pressure, and little change in respiration. Stimulation of the central end results in immediate apnea, a moderate fall in blood pressure, and little change in heart rate. Electrical stimulation of the dorsal medulla produces short-latency bradycardia at points clustering in: (a) lateral dorsal motor nucleus, 0.5–1.0 mm rostral to the obex; (b) solitary tract; and (c) commissural nucleus of Cajal. Apnea frequently accompanies bradycardia except when elicited by stimulation of the dorsal motor nucleus. Hypotension always follows bradycardia, while hypertension accompanies tachycardia. These bradycardia responses are abolished by bilateral vagotomy and severly diminished when the ipsilateral vagus is cut or pharmacologically blocked. Beta-sympathetic blockade has no effect on the occurrence of bradycardia responses. It is concluded that an efferent cardioinhibitory region in the pigeon is localized in the lateral dorsal motor nucleus 0.5–1.0 mm rostral to the obex and that bradycardia elicited from the solitary tract and commissural nucleus result from stimulating afferents. These results correlate nicely with the localization of the cells of origin of vagal cardioinhibitory fibers based on retrograde degeneration experiments, and together the anatomical and physiological findings indicate a concentration of these neurons in the ventrolateral aspect of the dorsal motor nucleus approximately three-quarters of a millimeter rostral to the obex.
Early Onset Multiple Sclerosis: A Review for Nurse Practitioners

Research demonstrates that 3.5% to 5% of persons with multiple sclerosis (MS) present before the age of 18 years. MS can present in early childhood through adolescence and must be considered as a differential diagnosis in patients with motor impairment, sensory changes, and cognitive disability. The diagnosis of early-onset MS is based on findings from a complete history and physical examination along with brain and spine imaging. The purpose of this article is to review recent literature on early-onset MS and offer suggestions or clinical practice in the identification and management of patients with this debilitating disease.
SPLUNC1 regulation in airway epithelial cells: role of toll-like receptor 2 signaling

Background: Respiratory infections including Mycoplasma pneumoniae (Mp) contribute to various chronic lung diseases. We have shown that mouse short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein was able to inhibit Mp growth. Further, airway epithelial cells increased SPLUNC1 expression upon Mp infection. However, the mechanisms underlying SPLUNC1 regulation remain unknown. In the current study, we investigated if SPLUNC1 production following Mp infection is regulated through Toll-like receptor 2 (TLR2) signaling. Methods: Airway epithelial cell cultures were utilized to reveal the contribution of TLR2 signaling including NF-B to SPLUNC1 production upon bacterial infection and TLR2 agonist stimulation. Results: Mp and TLR2 agonist Pam3CSK4 increased SPLUNC1 expression in tracheal epithelial cells from wild type, but not TLR2 -/- BALB/c mice. RNA interference (short-hairpin RNA) of TLR2 in normal human bronchial epithelial cells under air-liquid interface cultures significantly reduced SPLUNC1 levels in Mp-infected or Pam3CSK4-treated cells. Inhibition and activation of NF-B pathway decreased and increased SPLUNC1 production in airway epithelial cells, respectively. Conclusions: Our data for the first time suggest that airway epithelial TLR2 signaling is pivotal in mycoplasmainduced SPLUNC1 production, thus improving our understanding of the aberrant SPLUNC1 expression in airways of patients suffering from chronic lung diseases with bacterial infections.
Training Older Adults to Access Health Information

Many older adults do not use health information available on the Internet. Older adults residing in affordable housing were taught to use the NIHSeniorHealth.gov Web site. Participants were predominantly African American women with limited education and income (N = 42). Outcomes included changes in computer and health Web site navigation skills. Results showed significant improvements for all demographic groups in both computer and Web site navigation (p < .001). Older minority adults with no prior computer experience were willing and able to learn to use health Web sites. Success factors included an instructor familiar with the community, peer training assistants, and a focus on new learner needs.
Preparation and polymerization of 1,5‐diamino‐2,4‐alkylenetrisilazanes

1,5-Diamino-2,4-ethylenehexamethyltrisilazane and related compounds were prepared by treating the corresponding chlorosilane intermediates with ammonia or an amine. When these monomers were heated in xylene solution at 140°C. in the presence of ammonium sulfate, linear silicon-nitrogen polymers were obtained with molecular weights in the range of 7,500–15,000. Elemental analyses, infrared spectra, and the physical properties of the polymers support the proposed structure and polymerization route.
Assessing the reliability of linear dynamic transformer thermal modelling

Improving the utilisation of transformers requires that the hot-spot and top-oil temperatures be predicted accurately. Using measured (noisy) data to derive equivalent linear dynamic thermal models yields performance that is superior to the ANSI standard model, but the reliability of these model coefficients must be assessed if the user is to have confidence in the model. By adding arbitrarily large amounts of data in the modelling process it was expected to make the reliability measures of these models arbitrarily small. When this did not happen, an investigation began that showed why there is a limitation to the accuracy of models derived from noisy data. It is also shown that a standard technique for assessing the reliability of model coefficients is invalid because of the absence of unmeasured driving variables. An alternative method for assessing transformer model reliability is provided.
Pre-RTL formal verification: an intel experience

During the recent development of a next-generation Intel processor, the project's formal verification team verified a new coherence protocol and portions of its RTL implementation against the protocol's specification within project deadlines. Typically, FV teams apply formal property verification (FPV) after RTL is coded and, though it continues to be an effective complement to pre-silicon validation, this late application prevents it from keeping pace with the continual complexity increases in hardware designs. Our discussion centers around how applying FV early in the development cycle of this processor enabled continual verification as the design progressed, culminating with the targeted RTL verification. We also present the languages and methodologies used, the reasons behind the choices, and where improvements can be made.
Mean platelet volume/platelet count ratio as a predictor of long-term mortality after non-ST-elevation myocardial infarction

Previous studies reported an association between elevated mean platelet volume (MPV) and post-myocardial infarction mortality. This study explores the association between long-term mortality after non-ST-segment elevation myocardial infarction (NSTEMI) and the peripheral blood platelet indices (i.e., the mean platelet volume (MPV), platelet count, and the MPV/platelet (MPV/P) ratio). Two physicians independently reviewed the data of 619 NSTEMI patients. The blood samples were drawn and analyzed within 1 h of admission, the second, and the last hospital days. Patients were stratified into equal tertiles according to the platelet count, MPV, and MPV/platelet ratio. The primary outcome, 4-year all-cause mortality, was compared among the platelet indices tertile models. According to MPV, platelet count, and MPV/platelet ratio tertile models, there was a trend of higher 4-year mortality for the lower and upper tertiles in comparison to the middle tertiles. However, only the admission MPV/platelet ratio tercile...
Folate and colon cancer: a fascinating puzzle we have yet to complete.

This is an exciting era for those of us whose interests lie in the clinical applications of folate metabolism. As recently as 10 years ago, the only consequence of inadequate folate status that was felt to be of clinical import was thought to be anemia. The past decade has shone considerable light on how naive we were to believe this. Definitive clinical intervention trials have now demonstrated that diminished folate status early in pregnancy leads to higher rates in the occurrence and recurrence of births complicated by neural tube defects. Conversely, folate supplementation in the critical few weeks surrounding conception leads to a 75-100% reduction in such births. These compelling observations have already prompted the government of the USA to require folate fortification of all uncooked cereal grains and similar considerations are underway in several other countries. Folate is also now being increasingly implicated as an agent that might be effective in the prevention of occlusive cardiovascular disease. Marginal decreases in folate status lead to incremental increases in serum homocysteine levels and a large body of epidemiologic studies indicates that very modest increases in the concentration of this amino acid serves as an independent risk factor for stroke, myocardial infarction and peripheral vascular disease. Folate supplementation leads to a prompt reduction in serum homocysteine levels. We do not yet know whether such an intervention reduces the incidence of cardiovascular events, although this question constitutes the essence of several large intervention trials whose results will be available in the next several years. The most speculative, but possibly the most provocative, of all the new public health applications of folate is its potential for cancer prevention. No fewer than 16 epidemiologic studies have now examined the relationship between folate status and the risk of developing neoplasms of the colon and the overwhelming consensus of these studies, indicate an inverse relationship between folate status and colorectal neoplasia (reviewed in 1). Regardless of how compelling epidemiologic data may be, however, it can never prove causality: proving Such causality lies instead in the realm of the prospective, controlled intervention trial. This issue of Clinical Nutrition contains the third published prospective intervention trial (2) designed to examine whether folate supplementation might serve as an effective
Derivation of a composite measure of embedded symptom validity indices.

Assessment of effort on cognitive testing has become a suggested standard in both forensic and clinical neuropsychological assessment. Both stand-alone and empirically derived embedded measures have been developed, however guidelines for combining several measures are not always available. This study used logistic regression analysis to derive a multivariable composite to detect suboptimal effort using scores extracted from commonly administered neuropsychological tests. A model predicting suboptimal effort, as defined by performance on the Medical Symptom Validity Test, was created with 124 participants using variables from the California Verbal Learning test 2nd edition, Rey Complex Figure Test and the Wechsler Memory Scale 3rd edition. The model reliably predicted suboptimal effort (χ2 = 44.37, p < .001) with excellent discrimination (AUC = .84).
Epicardium Formation as a Sensor in Toxicology

Zebrafish (Danio rerio) are an excellent vertebrate model for studying heart development, regeneration and cardiotoxicity. Zebrafish embryos exposed during the temporal window of epicardium development to the aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibit severe heart malformations. TCDD exposure prevents both proepicardial organ (PE) and epicardium development. Exposure later in development, after the epicardium has formed, does not produce cardiac toxicity. It is not until the adult zebrafish heart is stimulated to regenerate does TCDD again cause detrimental effects. TCDD exposure prior to ventricular resection prevents cardiac regeneration. It is likely that TCDD-induced inhibition of epicardium development and cardiac regeneration occur via a common mechanism. Here, we describe experiments that focus on the epicardium as a target and sensor of zebrafish heart toxicity.
Open Source AI

Machines significantly more intelligent than humans will require changes in our legal and economic systems in order to preserve something of our human values. An open source design for artificial intelligence (AI) will help this process by discouraging corruption, by enabling many minds to search for errors, and by encouraging political cooperation. The author's experience developing open source software provides anecdotal evidence for the healthy social effects of open source development.
Characterization of the in situ structural and interfacial properties of the cationic hydrophobic heteropolypeptide, KL4, in lung surfactant bilayer and monolayer models at the air-water interface: implications for pulmonary surfactant delivery.

This study examines the various equilibrium in situ secondary structures of the pharmaceutical heteropolypeptide, KL4, in the solid state, in solution, and in the monolayer state alone and mixed with dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylglycerol (POPG). In situ surface circular dichroism spectroscopy, using a method first reported by Damodaran (Damodaran, S. Anal. Bioanal. Chem. 2003, 376, 182-188), of equilibrated KL4, DPPC/KL4, POPG/KL4, and DPPC/POPG/ KL4 monolayers at the air-water interface was used to examine the in situ two-dimensional conformation of KL4. Gravimetric vapor sorption by solid KL4 was used to analyze the effects of water molecules on the conformation of KL4 when confined as a monolayer at the surface of water. Solid-state KL4 conformation was determined by X-ray powder diffraction (XRPD). The equilibrium interfacial and spreading properties were measured at 25 °C, 37 °C, and 45 °C using the Wilhelmy plate method and Langmuir film balance. Equilibrium phase transition temperatures were measured using differential scanning calorimetry (DSC). It was found that solid-state KL4, which takes up very little water, exhibits � -sheet and R-helix secondary structures, whereas KL4 in solution appears to exist only as an R-helix. KL4 forms a stable, insoluble monolayer, exhibiting � -sheet and aperiodic structures. These structures provide KL4, when confined in two-dimensions, the structural flexibility to maximize favorable cationic lysine-water interactions and favorable leucine-leucine hydrophobic and van der Waals interactions; while effectively "shielding" the leucine residues away from water. In DPPC/KL4 monolayers, KL4 retains its native � -sheet and aperiodic structures, consistent with phase separation of DPPC and KL4 in bilayers and monolayers. In POPG/KL4 monolayers, KL4 exhibits an increase in aperiodic secondary structures (loss of � -sheet) to maximize favorable electrostatic interactions, consistent with the observed negative deviations from ideal monolayer mixing.