cssi/SciSciGPT-SciSciNet huggingface dataset:
Ranolazine inhibits shear sensitivity of endogenous Na+ current and spontaneous action potentials in HL-1 cells.

NaV1.5 is a mechanosensitive voltage-gated Na+ channel encoded by the gene SCN5A, expressed in cardiac myocytes and required for phase 0 of the cardiac action potential (AP). In the cardiomyocyte, ranolazine inhibits depolarizing Na+ current and delayed rectifier (IKr) currents. Recently, ranolazine was also shown to be an inhibitor of NaV1.5 mechanosensitivity. Stretch also accelerates the firing frequency of the SA node, and fluid shear stress increases the beating rate of cultured cardiomyocytes in vitro. However, no cultured cell platform exists currently for examination of spontaneous electrical activity in response to mechanical stimulation. In the present study, flow of solution over atrial myocyte-derived HL-1 cultured cells was used to study shear stress mechanosensitivity of Na+ current and spontaneous, endogenous rhythmic action potentials. In voltage-clamped HL-1 cells, bath flow increased peak Na+ current by 14 ± 5%. In current-clamped cells, bath flow increased the frequency and decay rate of AP by 27 ± 12% and 18 ± 4%, respectively. Ranolazine blocked both responses to shear stress. This study suggests that cultured HL-1 cells are a viable in vitro model for detailed study of the effects of mechanical stimulation on spontaneous cardiac action potentials. Inhibition of the frequency and decay rate of action potentials in HL-1 cells are potential mechanisms behind the antiarrhythmic effect of ranolazine.
Turbulent Suspension of Sediments in the Deep Sea

The high-energy benthic boundary layer experiment demonstrated the existence of high energy events capable of suspending large amounts of sediment at the base of the Nova Scotian Rise. The currents that cause these storms are episodic pulses of 25-35 cm s$^{-1}$ flows lasting four to seven days. The build up and decay of the currents is too rapid for local equilibrium of the suspended sediment distribution to be achieved. Therefore, a fully time-dependent model of the turbulent boundary layer and the suspended sediments was developed to describe the events in detail. The period of high flow is erosive for only a few hours. The surface erodible bed sediments are quickly removed. The dominant processes resulting in the development of the suspended sediment profile are then restricted to turbulent diffusion and entrainment. The depth of penetration of the suspended sediments into the water column is limited by stratification induced by suspended sediments. After the shear generated turbulence collapses most of the eroded sediment remained in suspension far above the expected \`equilibrium' height for a \`non-storm' turbulent boundary layer. Scaling arguments, and the model, show that fine clay particles kept in suspension by turbulent diffusion dominate settling during the low level turbulence present during `non-storm' conditions. Level 2 and 2${\textstyle\frac{1}{2}}$ energy closure models with stratification predict quite different structures of the nepheloid layer.
Reasoning about the height and location of a hidden object in 4.5- and 6.5-month-old infants.

Abstract The present experiments examined 6.5- and 4.5-month-old infants' ability to represent and to reason about the height and location of a hidden object. In Experiments 1 and 2, the infants were habituated to a screen that rotated back and forth through a 180°arc, in the manner of a drawbridge. Following habituation, a box was placed behind the screen, and the infants saw two test events. In one (possible event), the screen rotated until it reached the occluded box; in the other (impossible event), the screen rotated through either the top 80% or the top 50% of the space occupied by the box. The results indicated that (a) the 6.5-month-old infants were surprised when the screen rotated through the top 80%, but not the top 50%, of the box and (b) the 4.5-month-old infants failed to be surprised even when the screen rotated through the top 80% of the box (4.5-month-old infants do show surprise, however, when the screen rotates through the entire (100%) box (Baillargeon, 1987a)). Experiments 3 and 4 tested whether infants would be better at detecting that the screen rotated farther than it should if provided with a second, identical box to the side of the box behind the screen. This second box stood out of the screen's path and so remained visible throughout the test trials. The results indicated that with the second box present (a) the 6.5-month-old infants showed surprised when the screen rotated through the top 50% of the occluded box and (b) the 4.5-month-old infants were surprised when the screen rotated through either the top 80% or the top 50% of the box. The results of Experiment 5 revealed that the improvement in performance brought about by the second box disappeared when this box was no longer in the same fronto-parallel plane as the box behind the screen. Different models are considered to describe the impressive quantitative and qualitative physical reasoning abilities revealed by these findings.
Antecedent moisture and seasonal precipitation influence the response of canopy‐scale carbon and water exchange to rainfall pulses in a semi‐arid grassland

• The influences of prior monsoon-season drought (PMSD) and the seasonal timing of episodic rainfall ('pulses') on carbon and water exchange in water-limited ecosystems are poorly quantified. • In the present study, we estimated net ecosystem exchange of CO₂ (NEE) and evapotranspiration (ET) before, and for 15 d following, experimental irrigation in a semi-arid grassland during June and August 2003. Rainout shelters near Tucson, Arizona, USA, were positioned on contrasting soils (clay and sand) and planted with native (Heteropogon contortus) or non-native invasive (Eragrostis lehmanniana) C4 bunchgrasses. Plots received increased ('wet') or decreased ('dry’) monsoon-season (July–September) rainfall during 2002 and 2003. • Following a June 2003 39-mm pulse, species treatments had similar NEE and ET dynamics including 15-d integrated NEE (NEEpulse). Contrary to predictions, PMSD increased net C uptake during June in plots of both species. Greater flux rates after an August 2003 39-mm pulse reflected biotic activity associated with the North American Monsoon. Furthermore, August NEEpulse and ecosystem pulse-use efficiency (PUE(e) = NEE(pulse)/ET(pulse)) was greatest in Heteropogon plots. • PMSD and rainfall seasonal timing may interact with bunchgrass invasions to alter NEE and ET dynamics with consequences for PUE(e) in water-limited ecosystems.
Cutting Tool Performance of Laser Coated Diamond Coating and Diamond Facing Inserts

A study of cutting tool performance was conducted using poly-crystalline compact diamond (PCD); laser coated diamond coating tools, diamond facing tools, and C2 carbide inserts. The experiments are designed in a way that the PCD, CVD diamond coatings, diamond facing, and C2 carbide inserts can be tested and compared under the same cutting conditions. Although PCD is still the best cutting material of these inserts, the laser coated diamond and diamond-facing tools are closing the gap. The failure mode of a diamond coated insert can be described in the following steps. It starts with microattrition, during which gradually the coating on the cutting edge is worn out. Then the coating flakes off and the tool ceases to function. The diamond-facing insert has only the rake face treated. The surprisingly good performance of the diamond facing insert suggests that the tool's rake and flank face work as a team. Both diamond coating and diamond facing tools have good cutting performance and provide advantages in m...
Collaborative synthesis of visual analytic results

Visual analytic tools allow analysts to generate large collections of useful analytical results. We anticipate that analysts in most real world situations will draw from these collections when working together to solve complicated problems. This indicates a need to understand how users synthesize multiple collections of results. This paper reports the results of collaborative synthesis experiments conducted with expert geographers and disease biologists. Ten participants were worked in pairs to complete a simulated real-world synthesis task using artifacts printed on cards on a large, paper-covered workspace. Experiment results indicate that groups use a number of different approaches to collaborative synthesis, and that they employ a variety of organizational metaphors to structure their information. It is further evident that establishing common ground and role assignment are critical aspects of collaborative synthesis. We conclude with a set of general design guidelines for collaborative synthesis support tools.
Transforming growth factor β inhibits growth of more differentiated myeloid leukemia cells and retinoblastoma protein phosphorylation at serine 795

Transforming growth factor beta (TGF-beta) has been shown to be a specific inhibitor of early human myeloid progenitors. We show here that TGF-beta1 potentially inhibited not only the growth of primitive but also more mature myeloid leukemic cells. Surprisingly, those apparently more mature progenitor cells, such as MV4-11 and Mo7e cells, are very sensitive to the action of TGF-beta. The addition of TGF-beta1 to liquid cultures of these cells significantly inhibited their proliferation, with as much as 72% inhibition of growth of MV4-11 cells. The suppressive effect by TGF-beta1 was not reversed or prevented by granulocyte-macrophage colony-stimulating factor or interleukin 3 used to promote cell growth in TF-1a and MV4-11 cells. TGF-beta1 completely abolished the clonal growth of MV4-11 cells in soft agar and inhibited Mo7e, KG-1, K562, TF-1, and TF-1a colony growth by 99%, 90%, 63%, 53%, and 43%, respectively. The cells treated with TGF-beta1 showed progressive accumulation in the G1 phase of cell cycle. Maximal G1 arrest (93%) was observed in MV4-11 cells. Using anti-retinoblastoma protein (pRb) and anti-specific phosphorylated-pRb antibodies, we demonstrated that TGF-beta1 greatly inhibited pRb phosphorylation at serine 795 in MV4-11 and Mo7e cells. Taken together, our data suggest that the sensitivity of myeloid leukemic progenitor cells to growth inhibition by TGF-beta may not be inversely correlated with their maturation stage, and the inhibition of the cells appeared to be linked to the suppression of pRb phosphorylation at serine 795.
Stereochemical assignments of the 6‐phenyl‐2‐oxabicyclo[3.1.0]hexanes

Synthese des composes du titre a partir de dihydro-2,3 furanne et du chlorure de benzal en presence de t-butanolate de potassium; le derive chloro-6 du compose du titre obtenu est ensuite reduit par LiAlH 4 ; identification des isomeres endo et exo obtenus
Glutamine metabolism: Role in acid-base balance*

The intent of this review is to provide a broad overview of the interorgan metabolism of glutamine and to discuss in more detail its role in acid-base balance. Muscle, adipose tissue, and the lungs are the primary sites of glutamine synthesis and release. During normal acid-base balance, the small intestine and the liver are the major sites of glutamine utilization. The periportal hepatocytes catabolize glutamine and convert ammonium and bicarbonate ions to urea. In contrast, the perivenous hepatocytes are capable of synthesizing glutamine. During metabolic acidosis, the kidney becomes the major site of glutamine extraction and catabolism. This process generates ammonium ions that are excreted in the urine to facilitate the excretion of acids and bicarbonate ions that are transported to the blood to partially compensate the acidosis. The increased renal extraction of glutamine is balanced by an increased release from muscle and liver and by a decreased utilization in the intestine. During chronic acidosis, this adaptation is sustained, in part, by increased renal expression of genes that encode various transport proteins and key enzymes of glutamine metabolism. The increased levels of phosphoenolpyruvate carboxykinase result from increased transcription, while the increase in glutaminase and glutamate dehydrogenase activities result from stabilization of their respective mRNAs. Where feasible, this review draws upon data obtained from studies in humans. Studies conducted in model animals are discussed where available data from humans is either lacking or not firmly established. Because there are quantitative differences in tissue utilization and synthesis of glutamine in different mammals, the review will focus more on common principles than on quantification.
Tense and temporally neutral paraphrase

(1975). Tense and temporally neutral paraphrase. Australasian Journal of Philosophy: Vol. 53, No. 1, pp. 28-35.
Artistic Expression Goes Green

The paper is a critical discussion of the rich and insightful final chapter of Mitchell Green’s Self-Expression. There, Green seeks to elucidate the compelling, but inchoate intuition that when we’re fully and most expertly expressing ourselves, we can ‘push out’ from within not just our inner representations, but also the ways that we feel. I question, first, whether this type of ‘qualitative expression’ is really distinct from the other expressive forms that Green explores, and also whether it’s genuinely ‘expressive’. I then scrutinize the nature of the ‘qualitative congruences’ that lie at the heart of Green’s theory; and I wonder whether they can play the role Green claims they can in providing a novel account of artistic expression.
Neurovascular compression and trigeminal neuralgia

N eurovascular compression (NVC) seems to play an important role in the genesis of trigeminal neuralgia. In fact, the theme of NVC is played out in a number of other cranial nerve syndromes, most notably hemifacial spasm s and glossopharyngeal neuralgia? That NVC is the cause of trigeminal neuralgia is supported by considerable circumstantial evidence as presented in the focus article. I happen to agree with Dr. Jannetta's hypothesis, and have stated so previously? However, this conclusion is not yet irrefutable. For one thing, weshould not make the mistake of confusing a strong pathologic association with an understanding of the etiology of trigeminal neuralgia. Available contemporary surgical observations certainly support the role for NVC in trigeminal neuralgia. It was, in fact, Gardner and Miklos 7 at the Cleveland Clinic who first conceived and described decompression of the trigeminal nerve for trigeminal neuralgia in 1959. Later, while a resident at UCLA, Dr. Jannetta worked with Rand 11 (personal communication, May 1993), with whom he performed the first microvascular decompression (MVD) for trigeminal neuralgia using a surgical microscope in 1966. A hypothetical mechanism for the pathophysiology of trigeminal neuralgia has recently been reiterated by Fromm. 6 However, until we have a better grasp of the neurophysiology of trigeminal neuralgia, ultimate conclusions regarding the origins of the disorder will remain elusive. Dr. Jannetta has made a major contribution to the management of trigeminal neuralgia and other cranial neuropathies. He was among the first neurosur-
Convergent series solution of nonlinear equations

Abstract The author's decomposition method [1] provides a new, efficient computational procedure for solving large classes of nonlinear (and/or stochastic) equations. These include differential equations containing polynomial, exponential, and trigonometric terms, negative or irrational powers, and product nonlinearities [2]. Also included are partial differential equations [3], delay-differential equations [4], algebraic equations [5], and matrix equations [6] which describe physical systems. Essentially the method provides a systematic computational procedure for equations containing any nonlinear terms of physical significance. The procedure depends on calculation of the author's A n , a finite set of polynomials [1,13] in terms of which the nonlinearities can be expressed. This paper shows important properties of the A n which ensure an accurate and computable convergent solution by the author's decomposition method [1]. Since the nonlinearities and/or stochasticity which can be handled are quite general, the results are potentially extremely useful for applications and make a number of common approximations such as linearization, unnecessary.
Mutant p62P392L Stimulation of Osteoclast Differentiation in Paget's Disease of Bone

Paget's disease of the bone (PDB) is an autosomal dominant trait with genetic heterogeneity, characterized by abnormal osteoclastogenesis. Sequestosome 1 (p62) is a scaffold protein that plays an important role in receptor activator of nuclear factor κB (RANK) signaling essential for osteoclast (OCL) differentiation. p62P392L mutation in the ubiquitin-associated (UBA) domain is widely associated with PDB; however, the mechanisms by which p62P392L stimulate OCL differentiation in PDB are not completely understood. Deubiquitinating enzyme cylindromatosis (CYLD) has been shown to negatively regulate RANK ligand-RANK signaling essential for OCL differentiation. Here, we report that CYLD binds with the p62 wild-type (p62WT), non-UBA mutant (p62A381V) but not with the UBA mutant (p62P392L) in OCL progenitor cells. Also, p62P392L induces expression of c-Fos (2.8-fold) and nuclear factor of activated T cells c1 (6.0-fold) transcription factors critical for OCL differentiation. Furthermore, p62P392L expression results in accumulation of polyubiquitinated TNF receptor-associated factor (TRAF)6 and elevated levels of phospho-IκB during OCL differentiation. Retroviral transduction of p62P392L/CYLD short hairpin RNA significantly increased TRAP positive multinucleated OCL formation/bone resorption activity in mouse bone marrow cultures. Thus, the p62P392L mutation abolished CYLD interaction and enhanced OCL development/bone resorption activity in PDB.
Treatment of medical complications in patients with brain tumors

Patients with primary brain tumors and those with cerebral metastases are at risk throughout their illness for several major medical problems, including vasogenic edema, seizures, and symptomatic venous thrombosis. In turn, the corticosteroids, anti-epileptic drugs, and anticoagulants used to treat these problems may produce significant adverse effects and result in important drug-drug interactions that may complicate chemotherapy. Although few Class I studies address any of these issues, guidelines can be offered to maximize quality of life and minimize hospital readmis-sions. Optimal management of brain edema involves minimizing corticosteroid use and tapering the steroid dose slowly to avoid steroid withdrawal symptoms. Prophylaxis of Pneumocystis pneumonia is necessary for patients requiring corticosteroids for more than 1 month. Anti-epileptic drugs (AEDs) should be avoided unless patients experi-ence seizures. If possible, non-CTY (P450) enzyme-inducing drugs should be chosen. AED levels should be obtained frequently during corticosteroid taper. Multimodality venous thrombosis prophylaxis should begin at the time of the original surgery with external leg compression and unfractionated subcutaneous heparin or a low molecular weight heparin (LMWH). Brain tumor patients with symptomatic venous thrombosis or pulmonary embolism can be anticoagulated safely with warfarin or with LMWH, and LMWHs are preferable from the standpoints of efficacy, safety, and convenience for long-term outpatient treatment of venous thrombosis. Clinicians should be aware of potential drug-drug interactions between prescribed AEDs and chemotherapy and pos-sible interactions with complementary and alternative therapies chosen by their patients. They also should be aware of interventions to minimize late sequelae of brain tumors and their treatment, including cognitive decline, depression, and increased stroke risk.
Ergonomic Job Analysis: A Structured Approach for Identifying Risk Factors Associated with Overexertion Injuries and Disorders

Abstract Overexertion injuries and disorders, such as low back pain, tendonitis, and carpal tunnel syndrome, are the leading cause of work-related disabilities and Workers' Compensation costs in the United States and other industrialized nations. These injuries and disorders have been associated with six generic categories of ergonomic risk factors which are found in a broad spectrum of manufacturing and service jobs: 1) forceful exertions, 2) awkward work postures, 3) localized contact stresses, 4) whole-body or segmental vibration, 5) temperature extremes, and 6) repetitive motions or prolonged activities. Once recognized and evaluated, ergonomic principles can be applied to reduce exposures to these risk factors as part of a comprehensive program to control over-exertion injuries. A structured job analysis procedure has been developed to assist occupational health and safety professionals in the recognition and evaluation of exposures to ergonomic stresses in the workplace. This procedure is based on s...
Thermal expansion, thermal conductivity, and heat capacity measurements at Yucca Mountain, Nevada

Abstract A very extensive database for thermal properties of Yucca Mountain tuffs has been collected to characterize the Yucca Mountain, NV site. Cores from boreholes UE25 NRG-4, UE25 NRG-5, USW NRG-6, and USW NRG-7/7A, all drilled near the North Ramp of the Exploratory Studies Facility, were tested to determine thermal conductivity, thermal expansion, and specific heat. Specimens were tested from four thermal-mechanical units (TCw, PTn, TSw1, and TSw2) that included welded devitrified (TCw, TSw1, TSw2) and nonwelded vitric (PTn) tuff. The effects of moisture content, temperature, and composition were assessed. Petrologic data were obtained from 97 samples, all from USW NRG-6, to assess relationships between measured thermal properties and composition.
Oral contraceptives--possible mediation of side effects via an estrogen receptor in liver.

PIP: Most of the side effects of oral contraceptives may be caused by direct estrogen interaction in the liver resulting in alteration in liver function, including the synthesis of critical plasma proteins affecting the cardiovascular system. This study has succeeded in demonstrating an estrogen receptor in the mammalian liver. The liver receptors were found to consist, at least partly, of protein, and bound estrogens with high specificity. A strong binding affinity was indicated. The steroid hormones first bind to cytoplasmic receptors, after which the cytoplasmic receptor-steroid complex translocates from the cytoplasm to the nucleus and attaches to chromatin. Estrogen binding and translocation were shown in rat liver in vitro and in vivo. Minimizing the liver interaction thus might reduce the risk of side effects, but the estrogen-receptor function in the hypothalmic-pituitary axis and in the endometrium would have to be maintained. Possible differences in receptor characteristics of the 2 organs might be exploited to reduce liver interaction and, at the same time, possibly improve therapeutic benefits. Studies of receptor characteristics in rats indicate that a higher dose of estrogen is required in the liver than in the uterus and other organs to induce at least some direct effects. There seems to be a possibility that the newer combined oral contraceptives, which contain lower amounts of estrogen, ethinyl estradiol (reduced from 50 ug to 30 ug), and progestin, might produce smaller changes in estrogen-related plasma protein and at the same time achieve contraceptive effectiveness and regular menstrual bleeding patterns. Another possibility would be the future development or selection of another and safer estrogen.
Policing “The Patch”: Police Response to Rapid Population Growth in Oil Boomtowns in Western North Dakota:

This study examines police response to rapid population growth resulting from the oil boom in western North Dakota. This study uses methodological triangulation to examine how rapid population grow...
Two-level hybrid interpreter/native code execution for combined space-time program efficiency

A two-level programming model permits the applications programmer to write programs that benefit both from the code density of interpreted virtual machines and from the speed of native code execution. A well-defined boundary between the native code and the virtual machine facilitates the development of translators to be used at both levels.
Subtypes of Rumination in the Relationship Between Negative Life Events and Suicidal Ideation

The brooding and reflection forms of rumination were examined as mediators of the concurrent relationship between the impact of negative life events (INE), symptoms of depression, and suicidal ideation. An ethnically diverse sample of college undergraduates (N = 1,011) completed measures of negative life events and rumination, and they reported on their symptoms of depression and suicidal ideation. Brooding, but not reflection, partially mediated the INE-ideation relationship. Depression symptoms partially mediated the relationship between INE and suicidal ideation and between brooding and ideation. People who brood in response to negative life events may be vulnerable to thinking about suicide, partly due to symptoms of depression, but also as a result of brooding itself.
The Northern Charlotte belt North Carolina and South Carolina: A deformed composite batholith

The Charlotte belt in North Carolina and South Carolina, U.S.A. is characterized by numerous plutons with granitic to gabbroic composition that have intruded gneiss, schist, metavolcanic rocks, and metamorphosed mafic complexes (basalt, gabbro, and ultramafic rocks). The exposed rock constitutes a composite batholith which contains three superunits: (1) the Old Plutonic (metaquartz diorite, metagranodiorite, and metagabbro) approximately 550 my old; (2) the Concord-Salisbury (gabbro and granodiorite) approximately 400 my old; (3) the Landis ('big feldspar') granite approximately 300 my old. Geophysical and geologic studies suggest small bodies of granodiorite and mafic complexes intruding metavolcanic rocks, schist, and gneiss form the upper level of the batholith; a thick metagabbro sill penetrated by gabbro stocks and underlain by poikilitic gabbro and small bodies of syenite form the middle level; and a complex of metaquartz diorite and metagranodiorite intruded by Landis granites form the lowest level. Outcrop patterns and structural profiles based on gravity suggest the batholith forms an east-dipping monocline. The bimodal suite of gabbro and granodiorite plutons suggest a tensional tectonic environment ∼ 400 my ago, and negates subduction as the only mode of formation for the batholith.
Frequency agility in a ZigBee network for smart grid application

Smart grid is an intelligent power generation, distribution and control system. ZigBee, as wireless mesh networking scheme low in cost, power, data rate, and complexity, is ideal for smart grid applications. Unfortunately, almost all ZigBee channels are overlapped with wireless local area networks (WLAN) based on 802.11 specifications, resulting in significant service degradations in interference scenarios. We propose a frequency agility-based interference avoidance algorithm, which utilizes Energy Detection (ED) and active scan to perform smart channel selection. This algorithm can detect interference and adaptively switch nodes to “safe” channels to dynamically avoid WLAN interference. Our proposed scheme was empirically evaluated in terms of the packet error rate (PER) using a ZigBee and Wifi coexistence testbed, and the results were compared with our analytical results. The measurement results show the algorithm efficiently mitigates the effect of WiFi interference upon ZigBee networks.
Infrared antennas and frequency-selective surfaces

Radiofrequency components such as antennas, transmission lines, phased arrays, frequency-selective surfaces, reflectarrays and meanderline waveplates can be made to operate in the infrared using electron-beam lithography. Prof. Wolfe’s visionary leadership in the rather unique niche of “academic infrared” has been a source of inspiration to me throughout my career.
Issues in strategy for an irradiation program on fusion structural materials

Abstract This paper summarizes major issues in evaluating the use of advanced fusion devices as the principal radiation sources for the development of structural materials for commercial fusion reactors and focuses on work performed for the 1982 FED/INTOR study in the “Engineering Testing” task. The general objective of this task was to estimate the benefit for a DEMO reactor resulting from irradiation tests on structural materials in an engineering reactor (e.g. FED/INTOR). Some background information on radiation sources is also presented.
Potential Involvement of LOX-1 in Functional Consequences of Endothelial Senescence

Numerous studies have described the process of senescence associated with accumulation of oxidative damage, mutations and decline in proliferative potential. Although the changes observed in senescent cells are likely to result in significant phenotypic alterations, the studies on consequences of endothelial senescence, especially in relation to aging-associated diseases, are scarce. We have analyzed effects of senescence on the functions of endothelial cells relevant to the development of atherosclerosis including angiogenesis, adhesion, apoptosis and inflammation. In the course of progressing through the passages, human umbilical vein endothelial cells (HUVECs) displayed significant increase in size (+36% passage 12 vs. passage 4 , p<0.001) and reduction in both basal and VEGF-stimulated tube formation. The analysis of a scavenger receptor LOX-1, a key molecule implicated in atherogenesis, revealed a significant decline of its message (mRNA) and protein content in senescent endothelial cells (−33%) and in aortas of 50 wk (vs. 5 wk) old mice (all p<0.01). These effects were accompanied by a marked reduction of the basal expression of VCAM-1 and ICAM-1. Compared to early cultures, late passage HUVECs also exhibited nuclear translocation of NF-κB (p65) and reciprocal shifts in BAX and BCL2 protein content resulting in almost 2-fold increase in BAX/BCL2 ratio and 3-fold increase in apoptotic response to TNFα exposure (p<0.04). These changes in senescent endothelial cells are suggestive of aberrant responses to physiological stimuli resulting in a less permissive environment for tissue remodeling and progression of diseases requiring angiogenesis and cell adhesion in elderly, possibly, mediated by LOX-1.
Photonic Integration on the Hybrid Silicon Evanescent Device Platform

This paper reviews the recent progress of hybrid silicon evanescent devices. The hybrid silicon evanescent device structure consists of III-V epitaxial layers transferred to silicon waveguides through a low-temperature wafer bonding process to achieve optical gain, absorption, and modulation efficiently on a silicon photonics platform. The low-temperature wafer bonding process enables fusion of two different material systems without degradation of material quality and is scalable to wafer-level bonding. Lasers, amplifiers, photodetectors, and modulators have been demonstrated with this hybrid structure and integration of these individual components for improved optical functionality is also presented. This approach provides a unique way to build photonic active devices on silicon and should allow application of silicon photonic integrated circuits to optical telecommunication and optical interconnects.
Quality indicators for human milk use in very low-birthweight infants: are we measuring what we should be measuring?

Quality indicators for human milk use in very low-birthweight infants: are we measuring what we should be measuring?
Surgical management of thyrotoxicosis in children

thyroidism. The magnitude of these risks in childhood is unknown and this uncertainty has prompted most centers including ours to restrict this form of therapy to adults and the rare instances in children when the use of the other forms of treatment is contraindicated. Some very well-respected clinicians are using radioiodine in children. Their long-term resuhs will either vindicate or abolish the fears of the majority. Since long-term followup will be required to determine the answer to the most threatening fears, we must wait and decide among the other modalities at hand. Management of this disease process with drugs requires a prolonged period of administration and close supervision by the physician. At best only a 60-75 per cent incidence of permanent remission has been achieved. It has been the feeling of our institution that subtotal thyroidectomy would be the preferred form of therapy if the euthyroid state could be consistently attained with an absence of mortality and a minimum of m0rbidity.l Twenty-three years of experience at the University of Michigan Medical Center with bilateral subtotal thyroidectomy for thyrotoxicosis in children was reviewed in order to make this decision.
A logic framework for active contours on multi-channel images

We propose a mathematical framework for object detection using logic operations as a structure for defining multi-channel segmentation. The model combines object information from the different channels into any logic combination. We consider active contour methods which use one initial contour that would evolve from the information given in each channel simultaneously. Specific models are derived based on the single-channel region based ''active contours without edges'' [IEEE Trans. Image Process. 10 (2) (2001) 266] model. Numerical experiments show that the method is able to find general intersections, unions, and complements of the regions of objects of both synthetic and realistic images.
Testing the completeness of earthquake catalogues and the hypothesis of self-similarity

Self-similarity of the earthquake process is consistent with the observed linear b-value relation log (N) = a – bM, where N is the number of earthquakes with magnitude M. Deviations from linearity are believed to be due to statistical fluctuations because of the scarcity of events at large M, or from incompleteness because of a detection threshold at small M. Above some magnitude level, all local events are detected, because they exceed the noise background on the seismogram. As magnitude decreases, however, events go undetected as the seismic signal approaches the noise background. Thus more of the smallest events should be logged at night than during the day, because the cultural noise sources and winds are diminished at night, resulting in presumably quieter seismograms. Here we use this day-to-night noise modulation to develop a completeness test for earthquake catalogues; catalogues that indicate no significant modulation are considered complete. We test three catalogues and show that the completeness magnitude can be different from the magnitude at which the b-value departs from linearity. In particular, catalogues that show significant deviations in linearity at small M but are otherwise complete, are at odds with the hypothesis of earthquake self-similarity.
Ultrastructural study of lesions in gills of a marine shrimp exposed to cadmium1

Pathologic black gills of pink shrimp, Penaeus duorarum , exposed to 763 μg/l of cadmium chloride for 15 days were studied with transmission electron microscopy and were compared with normal gills of control pink shrimp. Local as well as extensive areas of cell death and necrosis were found in the distal gill filaments of black gills from cadmium-exposed shrimp. It is proposed that necrosis of specialized epithelial cells and septum cells in black gill filaments and contiguous nonblack gill tissue could cause osmoregulatory, detoxifying, and respiratory dysfunction in crustacea, particularly in individuals undergoing environmental stress such as salinity fluctuation.
Folding Landscapes of the Alzheimer Amyloid-β(12-28) Peptide

The energy landscape for folding of the 12-28 fragment of the Alzheimer amyloid β (Aβ) peptide is characterized using replica-exchange molecular dynamics simulations with an all-atom peptide model and explicit solvent. At physiological temperatures, the peptide exists mostly as a collapsed random coil, populating a small fraction (less than 10%) of hairpins with a β-turn at position V18F19, with another 10% of hairpin-like conformations possessing a bend rather than a turn in the central VFFA positions. A small fraction of the populated states, ∼14%, adopt polyproline II (PPII) conformations. Folding of the structured hairpin states proceeds through the assembly of two locally stable segments, VFFAE and EDVGS. The interactions stabilizing these locally folded structural motifs are in conflict with those stabilizing the global fold of A12-28, a signature of underlying residual frustration in this peptide. At increased temperature, the population of both β-strand and PPII conformations diminishes in favor of β-turn and random-coil states. On the basis of the conformational preferences of Aβ 12-28 monomers, two models for the molecular structure of amyloid fibrils formed by this peptide are proposed.
Coiled tube membrane bioreactor for cultivation of hybridoma cells producing monoclonal antibodies.

Abstract A coiled tube membrane reactor was developed for the cultivation of mouse—mouse hybridoma cells producing monoclonal antibodies. The cell and antibody concentrations obtained in the membrane reactor were higher than that obtained in a batch spinner flask without a membrane. A mathematical model has been developed to describe the membrane transport coupled growth and product formation, and the physical and kinetic constants of the system were determined.
Adult presentation of spinal dysraphism and tandem diastematomyelia

Abstract Background context Diastematomyelia is a split-cord malformation often accompanied by other cord or column anomalies. Purpose To report on an adult patient with diastematomyelia and discuss the embryological basis and related developmental sequelae of this split-cord malformation. Study design Case report. Methods A summary of the management of a 54-year-old woman with recent clinical symptomatology related to an undiagnosed split-cord malformation is presented with accompanying literature review. Results A rare adult presentation of diastematomyelia with accompanying intradural extramedullary epidermoid tumor was repaired with resection of the soft-tissue mass and excision of the fibro-osseous septum. Conclusion Initial presentation of diastematomyelia is rarely seen in adults; accompanying pathology includes scoliosis, tethered cord, and intradural tumors. Effective treatment involves identification of the primary pathology.
G protein-coupled adenosine (P1) and P2Y receptors: ligand design and receptor interactions

The medicinal chemistry and pharmacology of the four subtypes of adenosine receptors (ARs) and the eight subtypes of P2Y receptors (P2YRs, activated by a range of purine and pyrimidine mono- and dinucleotides) has recently advanced significantly leading to selective ligands. X-ray crystallographic structures of both agonist- and antagonist-bound forms of the A2AAR have provided unprecedented three-dimensional detail concerning molecular recognition in the binding site and the conformational changes in receptor activation. It is apparent that this ubiquitous cell signaling system has implications for understanding and treating many diseases. ATP and other nucleotides are readily released from intracellular sources under conditions of injury and organ stress, such as hypoxia, ischemia, or mechanical stress, and through channels and vesicular release. Adenosine may be generated extracellularly or by cellular release. Therefore, depending on pathophysiological factors, in a given tissue, there is often a tonic activation of one or more of the ARs or P2YRs that can be modulated by exogenous agents for a beneficial effect. Thus, this field has provided fertile ground for pharmaceutical development, leading to clinical trials of selective receptor ligands as imaging agents or for conditions including cardiac arrhythmias, ischemia/reperfusion injury, diabetes, pain, thrombosis, Parkinson’s disease, rheumatoid arthritis, psoriasis, dry eye disease, pulmonary diseases such as cystic fibrosis, glaucoma, cancer, chronic hepatitis C, and other diseases.
A Gas-Filled Channel Converter for Fast Coincidence Cameras

The construction of a mosaic of very small proportional counters consisting of high-atomic-number cathodes with conventional thin axial wire anodes was previously proposed1 for improvement of the time resolution and data rate of multiwire positron cameras and similar devices which are useful in medical diagnosis. In this paper, we show that the physical construction and electrical connections of the mosaic described are simpler than anticipated, and that manufacturing prospects compare favorably with those for multiwire chambers. The performance data of prototypes will be reported in a forthcoming issue of this journal.
Second Language Acquisition of Relative Clauses

One of the authors of this commentary conducted her dissertation research (Gass, 1979) on relative clause (RC) acquisition and, with the exception of a pedagogical intervention study (Gass, 1982), has since then participated in the discussion of RC acquisition only from afar. Therefore, the opportunity to provide commentary is particularly welcome. The framework adopted in Gass' earlier work was the earliest formulation of the Keenan and Comrie (1977) noun phrase accessibility hierarchy (NPAH). In what follows, we build on and extend that earlier work within the context of SLA.
Clinical Neurologic and Developmental Studies after Cardiac Surgery Utilizing Hypothermic Circulatory Arrest and Cardiopulmonary Bypass

The dramatic reduction in surgical mortality associated with repair of congenital heart anomalies in recent decades has been accompanied by a growing recognition of adverse neurologic sequelae in some survivors. Central nervous system (CNS) abnormalities may be a function of coexisting brain abnormalities (1, 2) or acquired events unrelated to surgical management (e.g., paradoxical embolus, brain infection, effects of chronic cyanosis) (3), but CNS insults appear to occur most frequently during or immediately after surgery. In particular, support techniques used during neonatal and infant cardiac surgery—cardiopulmonary bypass (CPB), profound hypothermia and circulatory arrest—have been implicated as important causes of brain injury. This paper will review the effects of CPB and deep hypothermic circulatory arrest (DHCA) on neurodevelopmental outcome.
Excretion of food-derived heterocyclic amine carcinogens into breast milk of lactating rats and formation of DNA adducts in the newborn.

The distribution, DNA adduction and excretion into breast milk of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were examined in lactating female F344 rats with 5 day old pups. Six hours after a single dose (10 mg/kg, p.o.) of radiolabeled IQ, MeIQx or PhIP to lactating dams, radioactivity in the dams was highest in the liver and kidney followed, in descending order, by the mammary gland, omental fat and brain. By 24 h after carcinogen administration, all tissues of the dams showed significantly reduced levels of radioactivity except for omental fat which changed only marginally from 6 to 24 h. 32P-Postlabeling analysis showed that the level of DNA adducts in mammary gland 6 h after dosing was 2.2, 0.7 and 0.2 adducts/10(7) nucleotides for PhIP, IQ and MeIQx respectively. In contrast, in hepatic DNA, the levels of IQ-DNA adducts (5.5 adducts/10(7) nucleotides) were 11-fold higher than those of PhIP or MeIQx. The stomach contents, liver, kidney and urine of pups nursed by dams given radiolabeled IQ, MeIQx or PhIP were radioactive, indicating that these carcinogens (and/or metabolites) were excreted into breast milk and absorbed by the pups. After a 6 h suckling period, the amount of PhIP-derived radioactivity in the stomach contents of the pups was approximately 10-fold higher than that seen with IQ or MeIQx. Urine from pups from the three groups was mutagenic in the Ames assay with Salmonella TA98 in the presence of an S9 activating system. IQ-, MeIQx- and PhIP-DNA adducts, at levels in the range of 0.25-0.46 adducts per 10(8) nucleotides, were detected in the livers of pups using the 32P-postlabeling method under intensification conditions. The results from this study indicate that breast milk is a route of exposure of the newborn to heterocyclic amines. The presence of DNA adducts in the tissues of pups further suggests that this route of exposure may have a carcinogenic consequence to the newborn.
Automating commutativity analysis at the design level

Two operations commute if executing them serially in either order results in the same change of state. In a system in which commands may be issued simultaneously by different users, lack of commutativity can result in unpredictable behaviour, even if the commands are serialized, because one user's command may be preempted by another's, and thus executed in an unanticipated state. This paper describes an automated approach to analyzing commutativity. The operations are expressed as constraints in a declarative modelling language such as Alloy, and a constraint solver is used to find violating scenarios. A case study application to the beam scheduling component of a proton therapy machine (originally specified in OCL) revealed several violations of commutativity in which requests from medical technicians in treatment rooms could conflict with the actions of a beam operator in a master control room. Some of the issues involved in automating the analysis for OCL itself are also discussed.
Human α1β3γ2L gamma‐aminobutyric acid type A receptors: High‐level production and purification in a functional state

Gamma-aminobutyric acid type A receptors (GABAARs) are the most important inhibitory chloride ion channels in the central nervous system and are major targets for a wide variety of drugs. The subunit compositions of GABAARs determine their function and pharmacological profile. GABAARs are heteropentamers of subunits, and (α1)2(β3)2(γ2L)1 is a common subtype. Biochemical and biophysical studies of GABAARs require larger quantities of receptors of defined subunit composition than are currently available. We previously reported high-level production of active human α1β3 GABAAR using tetracycline-inducible stable HEK293 cells. Here we extend the strategy to receptors containing three different subunits. We constructed a stable tetracycline-inducible HEK293-TetR cell line expressing human (N)–FLAG–α1β3γ2L–(C)–(GGS)3GK–1D4 GABAAR. These cells achieved expression levels of 70–90 pmol [3H]muscimol binding sites/15-cm plate at a specific activity of 15–30 pmol/mg of membrane protein. Incorporation of the γ2 subunit was confirmed by the ratio of [3H]flunitrazepam to [3H]muscimol binding sites and sensitivity of GABA-induced currents to benzodiazepines and zinc. The α1β3γ2L GABAARs were solubilized in dodecyl-d-maltoside, purified by anti-FLAG affinity chromatography and reconstituted in CHAPS/asolectin at an overall yield of ∼30%. Typical purifications yielded 1.0–1.5 nmoles of [3H]muscimol binding sites/60 plates. Receptors with similar properties could be purified by 1D4 affinity chromatography with lower overall yield. The composition of the purified, reconstituted receptors was confirmed by ligand binding, Western blot, and proteomics. Allosteric interactions between etomidate and [3H]muscimol binding were maintained in the purified state.